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OBJECTIVE: High-grade gliomas (HGGs) inevitably recur and progress despite resection and standard chemotherapies and radiation. Viral therapies have emerged as a theoretically favorable adjuvant modality that might overcome intrinsic factors of HGGs that confer treatment resistance. METHODS: The authors present the results of systematic searches of the MEDLINE and ClinicalTrials.gov databases that were performed for clinical trials published or registered up to July 15, 2020. RESULTS: Fifty-one completed clinical trials were identified that made use of a virus-based therapeutic strategy to treat HGG. The two main types of viral therapies were oncolytic viruses and viral vectors for gene therapy. Among clinical trials that met inclusion criteria, 20 related to oncolytic viruses and 31 to gene therapy trials. No oncolytic viruses have progressed to phase III clinical trial testing, although there have been many promising early-phase results and no reported cases of encephalitis or death due to viral therapy. Three phase III trials in which viral gene therapy was used have been completed but have not resulted in any FDA-approved therapy. Recent efforts in this area have been focused on the delivery of suicide genes such as herpes simplex virus thymidine kinase and cytosine deaminase. CONCLUSIONS: Decades of research efforts and an improving understanding of the immunomodulatory effects of viral therapies for gliomas are informing ongoing clinical efforts aimed at improving outcomes in patients with HGG. The available clinical data reveal varied efficacy among different virus-based treatment strategies.
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Glioblastoma , Glioma , Viroterapia Oncolítica , Virus Oncolíticos , Adulto , Glioblastoma/terapia , Glioma/terapia , Humanos , Recurrencia Local de NeoplasiaRESUMEN
OBJECTIVE: Metric tracking of grant funding over time for academic neurosurgeons sorted by gender informs the current climate of career development internationally for women in neurosurgery. METHODS: Multivariate linear trend analysis of grant funding awarded to neurosurgeons in the NIH and World Research Portfolio Online Reporting Tools Expenditures and Results (RePORTER) was performed. Traveling fellowships for international neurosurgery residents sponsored by the AANS and Congress of Neurological Surgeons (CNS) were also analyzed. RESULTS: Within the US, funding awarded to female neurosurgeons has remained static from 2009 to 2019 after adjusting for inflation and overall trends in NIH funding (ß = -$0.3 million per year, p = 0.16). Internationally, female neurosurgeons represented 21.7% (n = 5) of project leads for World RePORTER grants. Traveling fellowships are also an important building block for young international female neurosurgeons, of which 7.4% (n = 2) of AANS international traveling fellowships and 19.4% (n = 7) of AANS/CNS pediatrics international traveling fellowships are women. CONCLUSIONS: Over the past decade, funding has increased in neurosurgery without a concordant increase in funding awarded to women. Recognition of this trend is essential to focus efforts on research and career development opportunities for women in neurosurgery. Worldwide, female neurosurgeons head one-fifth of the funded project leads and constitute a minority of international traveling fellowships awarded by organized neurosurgery.
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Neurocirugia , Niño , Becas , Femenino , Humanos , Neurocirujanos , Estados UnidosRESUMEN
Functional neurological disorder is a condition in which a patient has physical findings that are not compatible with anatomical boundaries, have no structural substrate and are not representable of an established disease. General anaesthesia and surgery have been previously reported as precipitating factors for functional disorders and mostly involve dissociative (non-epileptic) seizures. We report a patient with no psychiatric history or prior abnormal examination who developed sudden onset functional tetraplegia and sensory disturbances immediately after elective surgery, and who was subsequently discharged home several days later after nearly complete resolution of neurologic deficits. We highlight the features of this syndrome, including its unique postoperative presentation, unusual resolution and absence of any identifiable psycho-dynamic mechanism. We also introduce the tripod sign as a useful clinical tool in identifying functional tetraplegia.
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Unidades de Cuidados Intensivos , Cuadriplejía , Trastornos Disociativos , Humanos , Cuadriplejía/etiología , ConvulsionesRESUMEN
OBJECTIVE: Conventional frame-based stereotactic systems have circumferential base frames, often necessitating deep brain stimulation (DBS) surgery in two stages: intracranial electrode insertion followed by surgical re-preparation and pulse generator implantation. Some patients do not tolerate awake surgery, underscoring the need for a safe alternative for asleep DBS surgery. A frame-based stereotactic system with a skull-mounted "key" in lieu of a circumferential base frame received US FDA clearance. The authors describe the system's application for single-stage, asleep DBS surgery in 8 patients at their institution and review its workflow and technical considerations. METHODS: Eight patients underwent DBS lead insertion and IPG implantation in a single surgical preparation under general anesthesia using the system. Postoperative CT imaging confirmed lead placement. RESULTS: Eight patients underwent implantation of 15 total leads targeting the ventral intermediate nucleus (4 patients), globus pallidus internus (GPi; 3 patients), and subthalamic nucleus (STN; 1 patient). Intraoperative microelectrode recording was conducted for GPi and STN targets. Postoperative CT imaging revealed a mean ± SD radial error of 1.24 ± 0.45 mm (n = 15 leads), without surgical complications. CONCLUSIONS: The stereotactic system facilitated safe and effective asleep, single-stage DBS surgery, maintaining traditional lead accuracy standards.
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Anestesia General , Estimulación Encefálica Profunda , Electrodos Implantados , Técnicas Estereotáxicas , Humanos , Estimulación Encefálica Profunda/métodos , Estimulación Encefálica Profunda/instrumentación , Masculino , Femenino , Persona de Mediana Edad , Anciano , Núcleo Subtalámico/cirugía , Enfermedad de Parkinson/terapia , Enfermedad de Parkinson/cirugía , Globo Pálido/cirugía , Globo Pálido/diagnóstico por imagen , Adulto , Tomografía Computarizada por Rayos XRESUMEN
Serotonin (5-HT) is a monoamine neurotransmitter in the peripheral, enteric, and central nervous systems (CNS). Within the CNS, serotonin is principally involved in mood regulation and reward-seeking behaviors. It is a critical regulator in CNS pathologies such as major depressive disorder, addiction, and schizophrenia. Consequently, in vivo serotonin measurements within the CNS have emerged as one of many promising approaches to investigating the pathogenesis, progression, and treatment of these and other neuropsychiatric conditions. These techniques vary in methods, ranging from analyte sampling with microdialysis to voltammetry. Provided this diversity in approach, inherent differences between techniques are inevitable. These include biosensor size, temporal/spatial resolution, and absolute value measurement capabilities, all of which must be considered to fit the prospective researcher's needs. In this review, we summarize currently available methods for the measurement of serotonin, including novel voltammetric absolute value measurement techniques. We also detail serotonin's role in various neuropsychiatric conditions, highlighting the role of phasic and tonic serotonergic neuronal firing within each where relevant. Lastly, we briefly review the present clinical application of these techniques and discuss the potential of a closed-loop monitoring and neuromodulation system utilizing deep brain stimulation (DBS).
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Trastorno Depresivo Mayor , Serotonina , Humanos , Estudios Prospectivos , Sistema Nervioso Central , NeurotransmisoresRESUMEN
BACKGROUND: Pituitary abscess is a rare clinical entity, typically precipitated by Staphylococcus, Pseudomonas, or Aspergillus infection. Although Nocardia species-associated central nervous system abscesses have been documented in immunocompromised patients, no case of Nocardia pituitary abscesses has been previously reported. OBSERVATIONS: A 44-year-old man presented with hemoptysis and was found to have a cavitary right lung nodule, which was presumed histoplasmosis, prompting antifungal treatment. Several months later, he developed panhypopituitarism. Magnetic resonance imaging identified a pituitary mass, which subsequently underwent transsphenoidal endoscopic biopsy. Infectious workup was negative, and the patient was discharged on intravenous ertapenem therapy. Over several months, he developed progressive headaches, and updated imaging confirmed interval enlargement of the mass with new cavernous sinus invasion. He underwent repeat endoscopic biopsy, which yielded positive cultures for Nocardia farcinica and prompted successful treatment with trimethoprim-sulfamethoxazole and linezolid. LESSONS: The current study highlights a previously unreported clinical entity, the first pituitary abscess attributable to Nocardia sp. or N. farcinica, which arose in a young, immunocompetent individual. Although rare, atypical infections represent an important component in the differential diagnosis for sellar mass lesions.
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OBJECTIVE: At present, females constitute less than 10% of neurosurgeons in the US, despite representing approximately half of all medical students. Multiple barriers have been described for females entering the neurosurgical field, particularly academic neurosurgery. Understanding the environment that female neurosurgeons face and any potential barriers preventing career advancement is needed to recruit, promote, and retain females in neurosurgery. METHODS: The gender composition of editorial boards for 5 high-impact neurosurgery journals was analyzed from 2000 to 2020. The names of editorial board members were obtained directly from the journal administration, physical copies of the published journal, or publicly available data through each journal's website. The gender, degrees, academic titles, H-index, and country were determined for each individual and statistical tests were performed to identify significant differences. RESULTS: Of the 466 identified individuals that served on at least one editorial board between 2000 and 2020, there were 36 females (7.7%) and 430 males (92.3%). There were no significant differences between males and females serving on multiple editorial boards. Most females possessed an additional graduate degree (58.3%), while only one-third of males (33.5%) obtained such a degree (p = 0.002). In addition, males had significantly higher average H-indices than females (p = 0.002). These trends were also observed when analyzing only US-based editorial board members. Although females were more likely overall to be identified as associate professors, males were more likely to be appointed as full professors (p = 0.001); this trend did not remain true in the US-based cohort. When analyzing the editorial boards for individual journals, all 5 journals experienced an increase of female representation since 2000 or since their inception after 2000. The highest proportion of females for a single journal was 27.3% in 2020. All other journals ranged from 11.0% to 13.5% in 2020. CONCLUSIONS: When entering the field of neurosurgery, females continue to face significant social and academic barriers. While the proportion of females on editorial boards for neurosurgery journals in 2020 is consistent with the proportion of practicing female neurosurgeons, there is a statistically significantly higher likelihood that females possess additional graduate degrees and lower H-indices compared to their male counterparts. The authors encourage neurosurgical journals to continue expanding female representation on editorial boards.
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INTRODUCTION: High-speed motor vehicle accidents (MVAs) are an important cause of brachial plexus injury (BPI). Some case reports have demonstrated shoulder seat belt use resulting in traction injuries to the brachial plexus. We used a national trauma registry to determine the association between seat belt use and brachial plexus injury in MVAs. METHODS: The authors queried the National Trauma Databank between 2016 and 2017 for patients with a hospital admission following an MVA. Cases with BPI were identified using International Classification of Diseases, Tenth Edition, Clinical Modification, diagnosis codes. Case-control matching by age and sex was performed to identify 2 non-BPI controls for every case of BPI. Multivariable conditional logistic regression adjusting for body mass index, alcohol use, and drug use was then performed to determine the adjusted association between safety equipment use (seat belt use and airbag deployment) and BPI. RESULTS: A total of 526,007 cases of MVAs were identified, of which 704 (0.13%) sustained a BPI. The incidences of BPI in patients were the following without any protective device (0.16%), with airbag deployment alone (0.08%), with seat belt use alone (0.08%), and with combined airbag deployment and seat belt use (0.07%). Following 1:2 case-control matching by age and sex and multivariable conditional logistic regression, seat belt use (odds ratio [OR] 0.55; 95% confidence interval [CI] 0.42-0.71; P < 0.001) and airbag deployment (OR 0.52; 95% CI 0.33-0.82; P = 0.004) were found to be associated with decreased odds for BPI, with the least odds observed with combined seat belt use and airbag deployment (OR 0.49; 95% CI 0.33-0.74; P = 0.001). CONCLUSIONS: Despite anecdotal evidence suggesting increased likelihood of BPI with shoulder seat belt use, case-control analysis from a national trauma registry demonstrated that both seat belt use and airbag deployment are associated with lower odds of sustaining BPIs in MVAs, with the greatest protective effect observed with combined use. Future studies adjusting for rider location (passenger vs. driver) and other potential confounders such as make, type and speed of vehicle may help further characterize this association.
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Accidentes de Tránsito/tendencias , Airbags/tendencias , Plexo Braquial/lesiones , Bases de Datos Factuales/tendencias , Cinturones de Seguridad/tendencias , Accidentes de Tránsito/prevención & control , Adulto , Airbags/normas , Estudios de Casos y Controles , Femenino , Humanos , Masculino , Persona de Mediana Edad , Cinturones de Seguridad/normas , Estados Unidos/epidemiología , Adulto JovenRESUMEN
Objectives Juvenile nasopharyngeal angiofibromas (JNAs) are uncommon tumors with an evolving treatment paradigm. The objective of this study was to compare our prior experience reported in 2005 with our most contemporary series to compare practice improvements and the impact of expanded endonasal procedures. Design Retrospective review comparing a contemporary 22 patients with JNA who underwent surgical management between 2005 and 2019, compared with a historical cohort of 65 patients from the same center. Results The most common presenting symptom was epistaxis (68%). The median maximum tumor diameter was 4.4 cm. All patients underwent preoperative embolization. An endoscopic endonasal approach (EEA) was used in 18 patients (82%), compared with 9% in the series prior to 2005. Gross total resection was achieved in all patients. The median estimated blood loss was 175 and 350 mL for EEA and open (transfacial) cases, respectively. Only two patients (9%) required a blood transfusion compared with 52% on the previous series. The median follow-up was 19 months. The overall recurrence rate was 9% in this series and 24% in the previous series. No patient required radiation therapy in follow-up compared with 3% in our historical cohort. Conclusion There have been significant changes regarding the management of patients with JNA compared with the previous Mayo Clinic experience. The EEA has become the preferred route over the transfacial approaches to treat JNA in selected patients who do not have intracranial extension. Preoperative embolization has aided in reducing the postoperative transfusion rates.
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OBJECTIVE: Patients with ankylosing spinal disorders (ASDs), including ankylosing spondylitis (AS) and diffuse idiopathic skeletal hyperostosis (DISH), have been shown to experience significantly increased rates of postoperative complications. Despite this, very few risk stratification tools have been validated for this population. As such, the purpose of this study was to identify predictors of adverse events and mortality in ASD patients undergoing surgery for 3-column fractures. METHODS: All adult patients with a documented history of AS or DISH who underwent surgery for a traumatic 3-column fracture between 2000 and 2020 were identified. Perioperative variables, including comorbidities, time to diagnosis, and number of fused segments, were collected. Three instruments, including the Charlson Comorbidity Index (CCI), modified frailty index (mFI), and Injury Severity Score (ISS), were computed for each patient. The primary outcomes of interest included 1-year mortality, as well as postoperative complications. RESULTS: A total of 108 patients were included, with a mean ± SD age of 73 ± 11 years. Of these, 41 (38%) experienced at least 1 postoperative complication and 22 (20.4%) died within 12 months after surgery. When the authors controlled for potential known confounders, the CCI score was significantly associated with postoperative adverse events (OR 1.20, 95% CI 1.00-1.42, p = 0.045) and trended toward significance for mortality (OR 1.19, 95% CI 0.97-1.45, p = 0.098). In contrast, mFI score and ISS were not significantly predictive of either outcome. CONCLUSIONS: Complications in spine trauma patients with ASD may be driven by comorbidity burden rather than operative or injury-related factors. The CCI may be a valuable tool for the evaluation of this unique population.
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BACKGROUND: Neurosurgery residency in the United States is highly sought after by many international medical graduates (IMGs), and the geographic distribution of IMG candidates who have successfully matched has not been quantitatively explored to date. The aim of this study was to highlight the countries in which successfully matched IMG residents obtained their medical degrees and the states of their respective residency destinations. METHODS: All available resident lists of approved neurosurgical residency programs within the United States with at least 7 years of history were reviewed for IMGs in the most currently updated rosters. Demographic and geographic characteristics were summarized. RESULTS: A total of 1393 current neurosurgical residents in U.S. residency programs were identified from 99 programs across 39 states. Of 1393 residents, 87 were IMGs (6%). The IMG contingent originated from 39 countries, the most common of which was Lebanon (n = 14/87 [16%]). The Middle East was the most represented geographic region (n = 23/87 [26%]). The states with the highest number of IMGs were Kentucky, New York, and Texas (all n = 7/87 [8%]). CONCLUSIONS: IMGs constitute a small but appreciable portion of current neurosurgical residents in U.S. training programs. Particular countries have contributed more IMGs to neurosurgical programs than others, and particular states have higher counts and proportions of IMG residents than others. These outcomes are not geographically homogeneous, and the mechanisms by which IMG applicants successfully match to U.S. neurosurgery programs require more biographic granularity to elucidate.