ABSTRACT Objective Post‐operative nausea and vomiting (PONV) is common following endoscopic skull base surgery despite multimodal prophylaxis and carries a risk of post‐operative bleeding and cerebrospinal fluid (CSF) leakage. This study aims to investigate if pre‐operative administration of the neurokinin‐1 (NK‐1) antagonist, aprepitant, reduces PONV in patients undergoing endoscopic skull base surgery. Methods A retrospective review of 58 patients undergoing endoscopic skull base surgery was performed. Demographic variables and clinical variables such as anesthesia type, procedural time, intraoperative CSF leak, and co‐administration of other antiemetics were collected. Primary outcome was PONV events, defined as the documentation of nausea and/or vomiting in the medical record or use of rescue antiemetic therapy. Post‐operative bleeding and CSF leaks were recorded. Univariate and multivariate analyses were conducted in R with the following covariates: co‐administered antiemetics, TIVA use, smoking status, ASA score, procedural duration, and intraoperative CSF leak. Results Of patients who received aprepitant, 42.9% developed PONV compared to 43.2% in the non‐aprepitant group. On univariate analysis, there was no difference in PONV (OR 0.98, p = 1.00), vomiting (OR 0.33, p = 0.30), or post‐operative bleeding (OR 0.87, p = 1.00) between groups. Multivariate regression showed no association between PONV and aprepitant (OR 0.52, p = 0.32). Subgroup analysis of patients undergoing transsphenoidal surgery showed no association of PONV and aprepitant (OR 0.45, p = 0.34). Conclusion PONV occurs in nearly half of patients undergoing endonasal skull base surgery. Pre‐operative administration of aprepitant was not associated with reduced risk of developing PONV. Level of Evidence 3.

OBJECTIVE:Meningiomas are typically benign, slow-growing tumors localized to the cranial or spinal regions, with less than 1% metastasizing systemically, posing a serious clinical challenge. This case series adds critically needed data to broaden existing knowledge and demonstrates that early molecular profiling may identify patients at risk for systemic metastasis, informing surveillance strategies and treatment decisions. METHODS:Between 2012 and 2024, we retrospectively reviewed patients with meningiomas from our institution's electronic medical record. Clinical data, including imaging, biopsy results, and surgical outcomes, were reviewed, focusing on genomic details, histopathology, disease progression, and treatment. RESULTS:We found 2888 patients with meningiomas, 5 of whom developed metastatic features, one Grade 2 atypical meningioma, and 4 Grade 3 anaplastic meningiomas. Metastases occurred to the scalp (1 case), parotid gland (1 case), vertebra (3 cases), liver (1 case), lungs (1 case), and neck (1 case). Imaging (computed tomography, magnetic resonance imaging, positron emission tomography-computed tomography) and biopsies confirmed origin of metastases. These patients received multiple surgical resections, chemotherapy, targeted therapy (everolimus, ixazomib, and tazemetostat), and localized radiation. Mutations in MTAP, BRCA-1-associated protein-1, CDKN2A/B, and H3K27me3 were identified. Despite aggressive treatment, 3 patients experienced disease progression and died, while the others showed partial response to therapy. Survival averaged 107 months from diagnosis, dropping to 24 months postmetastasis. CONCLUSIONS:Extra-central nervous system metastatic meningiomas pose significant diagnostic and therapeutic challenges. High-grade meningiomas are more likely to metastasize; early detection of metastatic spread is challenging. Our findings highlight the need for a multidisciplinary approach with close follow-up, especially in recurrent or high-grade meningiomas with distinct mutations.

Intracortical brain-computer interfaces (BCIs) can restore communication to people with vocal tract paralysis by decoding cortical activity during attempted speech into text. State-of-the-art systems pairing neural-to-phoneme decoders with phoneme-to-word language models have achieved word error rates (WERs) as low as 1%, but only after collecting thousands of sentences of training data. Shortening the data collection process would facilitate scaling this new technology by reducing the time from device implant to high-accuracy communication. Here we introduce a transformer-based decoder model trained jointly across six intracortical speech BCI participants. For every participant - regardless of sex, disease etiology, or attempted speaking strategy - a multi-user model decoded speech more accurately (over 50% lower relative WER on average) than models trained on individual users' data. Notably, the multi-user model could be finetuned on fewer than 200 sentences from a held-out user to achieve a WER below 7%. These results reveal how to pool intracortical data across people to yield more accurate, generalizable, and rapidly-deployable decoding models.

Traumatic brain injury (TBI) has systemic consequences for patients, including a serendipitous role in enhancing fracture healing. Although most polytraumatic injuries impair bone repair, TBI has been associated with accelerated fracture healing and excessive callus formation. This review explores the current understanding of brain-bone interaction and the mechanisms by which TBI may promote osteogenesis. Key contributing factors include an altered immune response, endocrine modulation, sympathetic signaling, neuropeptide signaling, increased osteogenic factors, and exosomal microRNAs. These components influence many elements of fracture healing, including macrophage polarization, osteoblast differentiation, angiogenesis, and suppression of osteoclast activity. Additionally, the overlap between mechanisms of neurogenic heterotopic ossification and fracture healing in the context of associated TBI will be reviewed. Despite substantial pre-clinical and clinical evidence supporting this phenomenon, its translation to therapeutic strategies remains limited. We will discuss future directions for fracture studies that consider the emerging mechanisms of TBI-induced accelerated fracture repair, the existing complexity and challenges in the field, and the potential role of the evidence in developing novel therapeutic options. Understanding these pathways holds promise for advancing fracture and complex musculoskeletal injury treatment, ultimately improving patient outcomes.

BACKGROUND AND OBJECTIVES:Glioblastoma (GBM) is the most common primary malignant brain tumor and is universally fatal. Human and laboratory studies have suggested lidocaine has anti-GBM efficacy. The objective of this study was to assess direct cytotoxicity as a possible mechanism of anti-GBM efficacy of lidocaine by quantifying the concentration of lidocaine in tumor tissue during resection. METHODS:Twelve patients with pathology-confirmed IDHwt GBM were included in this study. The study group received an intravenous bolus dose of 1.5 mg/kg IBW of lidocaine at induction of anesthesia followed by 2 mg/kg IBW/hr infusion. Craniotomy was performed in the standard fashion. Up to 3 fresh tumor specimens were collected hourly from each patient after confirmation of diagnosis by frozen section. Plasma samples were simultaneously collected. Lidocaine concentration was measured using mass spectroscopy. The maximum concentration of lidocaine (Cmax), time from bolus to maximum concentration (Tmax), and area under curve from 0 to 3 h (AUC) were calculated for each patient. Patients were followed for survival and adverse events. RESULTS:The median tumor specimen Cmax, Tmax, and AUC values were 333 ng/mL (range 226-555), 179 min (range 126-211), and 20,665 ng*min/mL (range 8003-55,426), respectively. Peak lidocaine concentration in tumor was reached in 6 of 11 cases (excluding one patient due to missing the 3rd sample). Median Cmax and Tmax for plasma samples were 1195 ng/mL (range 951-1475) and 191 min (range 156-211), respectively. Median overall survival was 308 days (95 % CI: 74-413). Two grade 3 adverse events occurred which were deemed to be unlikely related to the study intervention. CONCLUSION:While lidocaine infiltrates tumor tissue when administered intravenously during GBM surgery, concentrations do not reach levels previously demonstrated to inhibit tumor growth in in vitro studies (roughly 2*108 ng/mL lidocaine). Alternative mechanisms may explain previously observed improved outcomes with lidocaine administration in human studies.

Objective:This study aims to (1) develop an augmented reality (AR) navigation platform for craniomaxillofacial (CMF) and head and neck surgery; (2) apply it to a range of surgical cases; and (3) evaluate the advantages, disadvantages, and clinical opportunities for AR navigation. Study Design:A multi-center retrospective case series. Setting:Four tertiary care academic centers. Methods:A novel AR navigation platform was collaboratively developed with Xironetic and deployed intraoperatively using only a head-mounted display (Microsoft HoloLens 2). Virtual surgical plans were generated from computed tomography/magnetic resonance imaging data and uploaded onto the AR platform. A reference array was mounted to the patient, and the virtual plan was registered to the patient intraoperatively. A retrospective review of all AR-navigated CMF cases since September 2023 was performed. Results:Thirty-three cases were reviewed and classified as either trauma, orthognathic, tumor, or craniofacial. The AR platform had several advantages over traditional navigation including real-time 3D visualization of the surgical plan, identification of critical structures, and real-time tracking. Furthermore, this case series presents the first-known examples of (1) AR instrument tracking for midface osteotomies, (2) AR tracking of the zygomaticomaxillary complex during fracture reduction, (3) mandibular tracking in orthognathic surgery, (4) AR fibula cutting guides for mandibular reconstruction, and (5) integration of real-time infrared visualization in an AR headset for vasculature identification. Conclusion:While still a developing technology, AR navigation provides several advantages over traditional navigation for CMF and head and neck surgery, including heads up, interactive 3D visualization of the surgical plan, identification of critical anatomy, and real-time tracking.

BACKGROUND:Idiopathic normal-pressure hydrocephalus is a neurologic disorder characterized by impaired gait, balance, cognition, and bladder control in older adults. The disorder is treated with shunt surgery, but the effectiveness of shunting is unclear. METHODS:We conducted a double-blind, randomized, placebo-controlled trial involving participants selected for shunt surgery on the basis of gait-velocity improvement with cerebrospinal fluid (CSF) drainage. Participants were randomly assigned to an open-shunt valve setting (opening pressure, 110 mm of water) or a placebo valve setting (opening pressure, >400 mm of water) of a noninvasively adjustable shunt. The primary outcome was the change in gait velocity 3 months after surgery. Secondary outcomes were the change at 3 months in the Tinetti scale total score (range, 0 to 28; lower scores indicate worse gait and balance), Montreal Cognitive Assessment (MoCA) score (range, 0 to 30; lower scores indicate worse cognition), and Overactive Bladder Questionnaire score (range, 0 to 100; higher scores indicate worse urinary incontinence). RESULTS:A total of 99 participants underwent randomization and received the assigned intervention. At 3 months, gait velocity had increased in the open-shunt group (mean [±SD] change, 0.23±0.23 m per second; assessed in 49 participants) and was unchanged in the placebo group (mean change, 0.03±0.23 m per second; assessed in 49 participants), resulting in a treatment difference of 0.21 m per second (95% confidence interval, 0.12 to 0.31; P<0.001). A significantly greater improvement in the open-shunt group than the placebo group was seen for the Tinetti scale score (mean change, 2.9 points vs. 0.5 points; P = 0.003) but not the MoCA score (1.3 points vs. 0.3 points) or the Overactive Bladder Questionnaire score (-3.3 points vs. -1.5 points). The results regarding adverse events were mixed, with more participants in the placebo group reporting falls (46% vs. 24%), an equal percentage having cerebral bleeding (2% in both groups), and more participants in the open-shunt group having subdural bleeding (12% vs. 2%) and positional headaches (59% vs. 28%). CONCLUSIONS:Among participants with idiopathic normal-pressure hydrocephalus who had a response to temporary CSF drainage, shunting resulted in significant improvements at 3 months in gait velocity and a measure of gait and balance but not in measures of cognition or incontinence. (Funded by the National Institute of Neurological Disorders and Stroke and the Trial Innovation Network; PENS ClinicalTrials.gov number, NCT05081128.).

Children with mild traumatic brain injury (TBI) often receive unnecessary imaging studies, hospital admissions, and interhospital transfers leading to avoidable burdens to patients, caregivers, and health systems. The Brain Injury Guidelines (BIG) consider a non-displaced skull fracture as a BIG-2 injury warranting hospitalization. In our clinical experience, patients with simple isolated non-displaced linear skull fractures seldom develop TBI-related complications. In this study, we evaluated the need for hospital admission for simple isolated linear skull fractures by examining the occurrence of clinically important TBI (ci-TBI) and patient outcome. We performed a retrospective study evaluating pediatric TBI admissions from 2018 to 2023 using an institutional registry of TBI patients requiring neurosurgery consultation. Patients included in our study cohort were 17 years and younger at injury, had a head computed tomography with an isolated skull fracture and a Glasgow Coma Scale (GCS) of 14 to 15. We excluded patients who had an intracranial injury (ICI), fractures extending into the skull base, or crossing the sagittal sinus. We reviewed medical records to identify the presence of ci-TBI: ICI resulting in death, neurosurgical intervention, intubation for more than 24 h, or hospital admission for at least 2 nights due to TBI. Repeat imaging studies obtained were reviewed to assess the progression of injury and association with clinical deterioration. Patient outcome was evaluated with the Glasgow Outcome Score Extended (GOS-E) 6 months after injury. Univariable statistics were calculated for continuous variables and 95% confidence intervals were calculated using the Clopper-Pearson exact method for proportions that were very close to 0 or 1 and the Wilson score interval for small-to-moderate proportions. A total of 804 subjects were analyzed, and 402 (50.0%) patients had a BIG-2 injury. A total of 247 of these BIG-2 patients (61.4%) had a simple, non-displaced fracture, and no associated ICI; 198 of these patients (80.2%) were transferred from referring hospitals. In both primary admissions and transfers, no significant injury progression on imaging was noted, no neurosurgical intervention occurred, and no patient had ci-TBI (0/247; 95% CI: 0% to 1.5%). Six-month GOS-E was available in a subset (53.8%) of patients: 98.5% were discharged home and had a favorable outcome (defined as GOS-E 5 to 7). ci-TBI rarely develops in children with simple isolated non-displaced skull fractures indicating that hospital admission and inpatient observation may not be necessary. In the context of the BIG, these patients can be considered for re-classification to a BIG-1 injury, which can reduce interhospital transfer and admission rates following implementation, while maintaining patient safety. A revised BIG classification for pediatric injuries is proposed.

Background: Orbital roof fractures are often the result of high-velocity collisions and are seen in 1–9% of patients with craniofacial trauma. Although the majority of orbital roof fractures are displaced superiorly, a subset results in inferior displacement of fracture fragments, posing a risk for muscle/nerve entrapment and possible blindness. Many of these patients have severe traumatic brain injury (TBI) and, in addition to orbital fractures, also have elevated intracranial pressure (ICP). Management of depressed orbital roof fractures in the setting of severe TBI with elevated ICP represents a management dilemma. Case Description: Two cases of severe TBI with associated downward displacement of orbital roof fractures were reviewed. Both cases exhibited elevated ICP correlated with the degree of orbital roof fracture depression. Surgical intervention involving elevation and repair of the fractures was undertaken when there was a significant risk of injury to the extraocular muscles and/or the optic nerve due to the extent of the fracture depression. Conclusion: Depressed orbital roof fractures may migrate in response to changes in ICP. Serial computed tomography scans and eye examinations may aid with determining the need for and timing of surgical intervention.

Whereas traditional histology and light microscopy require multiple steps of formalin fixation, paraffin embedding, and sectioning to generate images for pathologic diagnosis, Microscopy using Ultraviolet Surface Excitation (MUSE) operates through UV excitation on the cut surface of tissue, generating images of high resolution without the need to fix or section tissue and allowing for potential use for downstream molecular tests. Here, we present the first study of the use and suitability of MUSE microscopy for neuropathological samples. MUSE images were generated from surgical biopsy samples of primary and metastatic brain tumor biopsy samples (n = 27), and blinded assessments of diagnoses, tumor grades, and cellular features were compared to corresponding hematoxylin and eosin (H&E) images. A set of MUSE-treated samples subsequently underwent exome and targeted sequencing, and quality metrics were compared to those from fresh frozen specimens. Diagnostic accuracy was relatively high, and DNA and RNA integrity appeared to be preserved for this cohort. This suggests that MUSE may be a reliable method of generating high-quality diagnostic-grade histologic images for neuropathology on a rapid and sample-sparing basis and for subsequent molecular analysis of DNA and RNA.

Cancers and neurological disorders are two major types of diseases in humans. We developed the concept called the “Aberrant Cell Cycle Disease (ACCD)” due to the accumulating evidence that shows that two different diseases share the common mechanism of aberrant cell cycle re-entry. The aberrant cell cycle re-entry is manifested as kinase/oncoprotein activation and tumor suppressor (TS) inactivation, which are associated with both tumor growth in cancers and neuronal death in neurological disorders. Therefore, some cancer therapies (e.g., kinase/oncogene inhibition and TS elevation) can be leveraged for neurological treatments. MicroRNA (miR/miRNA) provides a new style of drug-target binding. For example, a single tumor suppressor miRNA (TS-miR/miRNA) can bind to and decrease tens of target kinases/oncogenes, producing much more robust efficacy to block cell cycle re-entry than inhibiting a single kinase/oncogene. In this review, we summarize the miRNAs that are altered in both cancers and neurological disorders, with an emphasis on miRNA drugs that have entered into clinical trials for neurological treatment.

OBJECTIVE:The primary treatment for peripheral nerve tumors involves maximal surgical resection while preserving nerve function. Sodium fluorescein shows potential for enhancing the safety and efficacy of nerve tumor surgery. This review evaluates the advantages and limitations of sodium fluorescein in this context. METHODS:PubMed, EMBASE, Web-of-Science, and Scopus were searched following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses-scoping review guidelines to include studies reporting the use of sodium fluorescein in peripheral nerve tumors surgery. Intervention-related outcomes (i.e., extent of resection, clinical outcomes, complication rates, recurrence rates, and duration of surgery) were evaluated and summarized. RESULTS:A total of 4 studies encompassing 166 patients with 168 tumors were included. Patients were mostly female (98; 53.6%), 101 (69.2%), had sporadic (nonsyndromic) tumors, and at histopathology, 114 (67.9%) tumors were WHO grade-1 schwannomas. Gross total resection was achieved in 146 (86.9%) tumors. Postoperative complications were reported in 16 cases (10.2%%), none related to side effects of the fluorescent dye. High tumor fluorescence was reported in 150 (94.3%) tumors, while absent and low parent nerve fluorescence was reported in 121 (79.6%) and 27 (17.8%), respectively. The median duration of surgery was 51.5 (range: 24-92) minutes. CONCLUSIONS:Sodium fluorescein shows promise as assisting tool in nerve tumor surgery by facilitating differentiation among the tumor, parent nerve, and surrounding soft tissue. However, multicenter randomized controlled trials are necessary to determine its effect on extent of resection rates, clinical outcomes, postoperative complication rates, and surgical duration in comparison to current standard of care.

Abstract The objective of this study is to assess the pharmacokinetics of lidocaine penetration into tumor tissue during glioblastoma surgery. In-vitro studies of glioblastoma have demonstrated co-culture with lidocaine inhibits glioblastoma proliferation via inhibition of TRPM7 channels. TRPM7 is a transmembrane ion channel that modulates proliferation and migration in several human cancers. Scalp block with lidocaine during glioblastoma surgery has been associated with improved survival in human studies. Twelve patients were enrolled in this study. The study group received an intravenous bolus dose of 1.5 mg/kg IBW of lidocaine at induction of anesthesia followed by 2 mg/kg IBW/hr infusion of lidocaine. Craniotomy was performed in the standard fashion. A total of 3 fresh tumor specimens were collected hourly from each patient after confirmation of glioblastoma diagnosis by frozen section. Plasma samples were simultaneously collected for analysis. Lidocaine concentration was measured using mass spectroscopy. The maximum concentration of lidocaine (Cmax), time from bolus to maximum concentration (Tmax), and area under curve from 0-3 hours (AUC) were calculated for each patient. Patients were followed for survival and adverse events. The median tumor specimen Cmax, Tmax, and AUC values were 333 ng/dL (range 226-555), 179 min (range 126-211), and 20665 ng*min/dL (range 8003-55,426), respectively. Peak lidocaine concentration was reached in 6 of 12 cases. Median Cmax and Tmax for plasma samples were 1195 ng/dL (range 951-1475) and 191 min (range 156-211), respectively. Median overall survival was 308 days (range 74-413). Two grade 3 adverse events occurred which were deemed to be unlikely to be related to the study intervention. In conclusion, lidocaine infiltrates tumor tissue when administered intravenously during glioblastoma surgery. Concentrations do not reach levels previously demonstrated to inhibit tumor growth in in vitro studies (roughly 2*108 ng/dL lidocaine). Alternative mechanisms may explain previously observed improved outcomes with lidocaine administration in human studies.

Children with mild traumatic brain injury (mTBI) and intracranial injury (ICI) often receive unnecessary imaging and hospital admission, leading to avoidable burdens on patients and health systems. While most of these patients do not develop critical neurological injuries, identifying those at risk would allow for a more optimal determination of the appropriate level of initial emergency care. The Brain Injury Guidelines (BIG) were developed as a triage tool to identify adult patients with mTBI and ICI who can benefit from repeat imaging, hospital admission, or neurosurgical consultation. Here, we sought to validate BIG in children at a Level I trauma center and determine if the BIG algorithm can accurately identify which patients with mTBI/ICI have critical neurosurgical injuries. We hypothesize that the BIG can identify critical neurological injuries more accurately than the Glasgow Coma Scale (GCS) alone and that more severe injury according to BIG is associated with worse patient outcome. We retrospectively reviewed TBI admissions at a single center (2017-2023) using an institutional registry. Patients included (0-17 years) had an initial head computerized tomography scan with ICI and a GCS of 14-15. Patients were retrospectively classified into the BIG categories (BIG 1, 2, or 3). Medical records were reviewed to identify clinically important TBI (ciTBI): death, neurological deterioration, neurosurgical intervention, intubation >24 h, or hospital admission >48 h due to TBI. Repeat imaging studies obtained were evaluated for progression of injury. The incidence of clinically important TBI (ciTBI) and imaging progression were recorded and compared across BIG categories. Outcomes were evaluated using the Glasgow Outcome Score Extended (GOS-E) 6 months after injury. Univariable and chi-square tests were used to analyze comparisons. Overall, 804 subjects were included in the analysis of which 551 (68.5%) were transfers. Overall, 175 (21.8%) patients had a BIG 1, 402 (50.0%) a BIG 2, and 227 (28.2%) a BIG 3 injury. CiTBI occurred among 64 (8.0%) patients overall, and in 1 (0.6%), 4 (1.0%), and 59 (26.0%) of the BIG 1, 2, and 3 injuries (p < 0.0001). Progression on repeat imaging associated with neurological decline, neurosurgical intervention or resulting in additional evaluation was noted in 0 (0%), 2 (0.5%), and 41 (18.0%) of the BIG 1, 2, and 3 injuries (p < 0.001). Amongst 471 patients (58.6%) with available 6-month patient outcomes, 98% had a GOS-E >= 5 and no outcome difference between BIG categories was observed. Risk stratification of mild TBI using BIG allowed for reasonable identification of children who subsequently develop ciTBI, suggesting that BIG classification can aid in triage and management of patients who might benefit from neurosurgical consultation, repeat imaging, and potentially transfer to a dedicated trauma center. More severe injury according to BIG was not associated with a worse patient outcome.