Determining the effects of targeted high-definition transcranial direct current stimulation on reducing post-stroke upper limb motor impairments-a randomized cross-over study.

BACKGROUND: Stroke is one of the leading causes of death in the USA and is a major cause of serious disability for adults. This randomized crossover study examines the effect of targeted high-definition transcranial direct current transcranial brain stimulation (tDCS) on upper extremity motor recovery in patients in the post-acute phase of stroke recovery. METHODS: This randomized double-blinded cross-over study includes four intervention arms: anodal, cathodal, and bilateral brain stimulation, as well as a placebo stimulation. Participants receive each intervention in a randomized order, with a 2-week washout period between each intervention. The primary outcome measure is change in Motor Evoked Potential. Secondary outcome measures include the Fugl-Meyer Upper Extremity (FM-UE) score, a subset of FM-UE (A), related to the muscle synergies, and the Modified Ashworth Scale. DISCUSSION: We hypothesize that anodal stimulation to the ipsilesional primary motor cortex will increase the excitability of the damaged cortico-spinal tract, reducing the UE flexion synergy and enhancing UE motor function. We further hypothesize that targeted cathodal stimulation to the contralesional premotor cortex will decrease activation of the cortico-reticulospinal tract (CRST) and the expression of the upper extremity (UE) flexion synergy and spasticity. Finally, we hypothesize bilateral stimulation will achieve both results simultaneously. Results from this study could improve understanding of the mechanism behind motor impairment and recovery in stroke and perfect the targeting of tDCS as a potential stroke intervention. With the use of appropriate screening, we anticipate no ethical or safety concerns. We plan to disseminate these research results to journals related to stroke recovery, engineering, and medicine. TRIAL REGISTRATION: ClinicalTrials.gov NCT05479006 . Registered on 26 July 2022.

Metabolic tagging of extracellular vesicles and development of enhanced extracellular vesicle based cancer vaccines.

As key mediators of cellular communication, extracellular vesicles (EVs) have been actively explored for diagnostic and therapeutic applications. However, effective methods to functionalize EVs and modulate the interaction between EVs and recipient cells are still lacking. Here we report a facile and universal metabolic tagging technology that can install unique chemical tags (e.g., azido groups) onto EVs. The surface chemical tags enable conjugation of molecules via efficient click chemistry, for the tracking and targeted modulation of EVs. In the context of tumor EV vaccines, we show that the conjugation of toll-like receptor 9 agonists onto EVs enables timely activation of dendritic cells and generation of superior antitumor CD8+ T cell response. These lead to 80% tumor-free survival against E.G7 lymphoma and 33% tumor-free survival against B16F10 melanoma. Our study yields a universal technology to generate chemically tagged EVs from parent cells, modulate EV-cell interactions, and develop potent EV vaccines.

Refractory seizures secondary to radiation-induced focal cortical dysplasia/neuronal gigantism: illustrative case.

BACKGROUND: Focal cortical dysplasia is a structural cause of drug-resistant epilepsy commonly identified in childhood. In rare cases, radiation-induced injury has led to radiation-induced cortical dysplasia, also known as "focal neuronal gigantism." OBSERVATIONS: The authors present a 53-year-old woman with recurrent status epilepticus events after she had radiation therapy and surgery for a left frontal meningioma several years prior. Imaging revealed findings consistent with radiation necrosis and possible recurrence. The patient's status epilepticus events required escalating therapies to manage. Scalp electroencephalography indicated that the seizure's origin was in the left hemisphere. A craniotomy was performed to remove the left frontal lesion, and histopathology was consistent with radiation-induced focal cortical dysplasia/neuronal gigantism. The patient's seizures ceased following the surgery, and she remains on maintenance antiseizure medications. LESSONS: Radiation-induced focal cortical dysplasia/neuronal gigantism is an incredibly rare complication of therapy. However, it warrants consideration in the context of radiation necrosis and intractable epilepsy.

The neurosurgeon workforce: a geographical gender-focused analysis of the trends in representation of neurosurgeons and choices in training over 70 years.

OBJECTIVE: Neurosurgeons frequently move throughout their careers, with moves driven by personal and professional factors. In this study, the authors analyzed these migration trends through a dynamic migratory map and statistical review, with a particular focus on differences in education and practice patterns between male and female neurosurgeons. METHODS: A list containing all board-certified and -affiliated US neurosurgeons practicing in 2019 was obtained from the American Association of Neurological Surgeons. The list was augmented to include demographic and location information for medical school, residency, fellowship(s), and current practice for all neurosurgeons with publicly available data. Migration heatmaps were generated, and migration patterns over 10-year intervals were plotted. A web tool was additionally created to allow for dynamic visualization of this database. RESULTS: The database included 5307 neurosurgeons with a mean age of 57.2 ± 11.3 years. The female population made up 8.93% of all neurosurgeons, and were found to be more likely to complete fellowships than their male counterparts, at 54.2% and 39.1%, respectively (p < 0.0001). A total of 39.5% of all neurosurgeons completed at least one fellowship. A large proportion of currently practicing US neurosurgeons completed medical school internationally in the 1990s. Recently, there has been a trend in neurosurgeons choosing to practice in the South, emigrating from the Northeast and the Western US Census regions. By population, the Western US region trained the fewest neurosurgeons at 1 per 115,000 residents, and the Northeastern US region trained the most at 1 per 49,000. The web tool provides a simple interface to visualize the database on a world map. CONCLUSIONS: Diversity, equity, and inclusion in neurosurgery have been a strong point of discussion in recent literature, with neurosurgeons comprising one of the most gender-disparate workforces in the US medical system. This study provides additional metrics to assess these disparities to help motivate further action toward a larger, more diverse neurosurgical community.

The State of Machine Learning in Outcomes Prediction of Transsphenoidal Surgery: A Systematic Review.

The purpose of this analysis is to assess the use of machine learning (ML) algorithms in the prediction of postoperative outcomes, including complications, recurrence, and death in transsphenoidal surgery. Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we systematically reviewed all papers that used at least one ML algorithm to predict outcomes after transsphenoidal surgery. We searched Scopus, PubMed, and Web of Science databases for studies published prior to May 12, 2021. We identified 13 studies enrolling 5,048 patients. We extracted the general characteristics of each study; the sensitivity, specificity, area under the curve (AUC) of the ML models developed as well as the features identified as important by the ML models. We identified 12 studies with 5,048 patients that included ML algorithms for adenomas, three with 1807 patients specifically for acromegaly, and five with 2105 patients specifically for Cushing's disease. Nearly all were single-institution studies. The studies used a heterogeneous mix of ML algorithms and features to build predictive models. All papers reported an AUC greater than 0.7, which indicates clinical utility. ML algorithms have the potential to predict postoperative outcomes of transsphenoidal surgery and can improve patient care. Ensemble algorithms and neural networks were often top performers when compared with other ML algorithms. Biochemical and preoperative features were most likely to be selected as important by ML models. Inexplicability remains a challenge, but algorithms such as local interpretable model-agnostic explanation or Shapley value can increase explainability of ML algorithms. Our analysis shows that ML algorithms have the potential to greatly assist surgeons in clinical decision making.

Traumatic Brain Injury Mortality and Correlates in Low- and Middle-Income Countries: A Meta-Epidemiological Study.

BACKGROUND: It is estimated that up to 69 million people per year experience traumatic brain injury (TBI) with the highest prevalence found in low- and middle-income countries (LMICs). A paucity of data suggests that the mortality rate after severe TBI is twice as high in LMICs than in high-income countries. OBJECTIVE: To analyze TBI mortality in LMICs and to evaluate what country-based socioeconomic and demographic parameters influence TBI outcomes. METHODS: Four databases were searched for the period January 1, 2002, to January 1, 2022, for studies describing TBI outcomes in LMICs. Multivariable analysis was performed using multivariable linear regression, with the outcome as the pooled mortality by country and the covariates as the adjusted parameters. RESULTS: Our search yielded 14 376 records of which 101 were included in the final analysis, totaling 59 197 patients and representing 31 LMICs. The pooled TBI-related mortality was 16.7% (95% CI: 13.7%-20.3%) without significant differences comparing pediatrics vs adults. Pooled severe TBI-related mortality was significantly higher than mild. Multivariable analysis showed a significant association between TBI-related mortality and median income ( P = .04), population percentage below poverty line ( P = .02), primary school enrollment ( P = .01), and poverty head ratio ( P = .04). CONCLUSION: TBI-related mortality in LMICs is 3-fold to 4-fold higher than that reported in high-income countries. Within LMICs, parameters associated with poorer outcomes after TBI include factors recognized as social determinants of health. Addressing social determinants of health in LMICs might expedite the quest to close the care delivery gap after TBI.

Efficacy of deep brain stimulation for the treatment of anorexia nervosa: a systematic review and network meta-analysis of patient-level data.

OBJECTIVE: Deep brain stimulation (DBS) has been approved as a therapy for movement disorders and obsessive-compulsive disorder. Recently, DBS has been studied in patients with anorexia nervosa (AN), which is a debilitating and life-threatening psychiatric disorder. Several stimulation locations have been tested without a clear indication of the best region. In this systematic review and network meta-analysis, the authors used patient-level data to identify stimulation targets with the greatest evidence for efficacy in increasing body mass index (BMI). METHODS: A systematic search was performed on or before August 4, 2022, using PubMed/MEDLINE, Ovid, and Scopus. Articles were included if patient-level data were presented, patients were diagnosed with AN and treated with DBS, and 6 months or more of postoperative follow-up data were reported. Quality and risk of bias were assessed with the NIH assessment tools. Patient data were collected and stratified by stimulation location. A network meta-analysis was performed. This review was written in accordance with PRISMA guidelines for systematic reviews. RESULTS: Eleven studies consisting of 36 patients were included. The mean age and BMI at the time of surgery were 38.07 (SD 11.64) years and 12.58 (SD 1.4) kg/m2, respectively. After 6 months of DBS, a significant difference in percentage change in BMI was found between the nucleus accumbens and subcallosal cingulate cortex (SCC) (SMD 0.78; 95% CI 0.10, 1.45) and between the SCC and ventral anterior limb of the internal capsule (SMD -1.51; 95% CI -2.39, -0.62). Similarly, at 9-12 months, a significant difference in percentage change in BMI was found between the SCC and ventral anterior limb of the internal capsule (SMD -1.18; 95% CI -2.21, -0.15). With hierarchical ranking, this study identified SCC as the most supported stimulation location for BMI change at 6 and 9-12 months (P-scores 0.9449 and 0.9771, respectively). CONCLUSIONS: Several DBS targets have been tested for AN, and this study identified the SCC as the most supported region for BMI change. However, further studies with blinded on/off periods are necessary to confirm this finding.

Differentiating radiation necrosis from tumor recurrence: a systematic review and diagnostic meta-analysis comparing imaging modalities.

PURPSOSE: Cerebral radiation necrosis (RN) is often a delayed phenomenon occurring several months to years after the completion of radiation treatment. Differentiating RN from tumor recurrence presents a diagnostic challenge on standard MRI. To date, no evidence-based guidelines exist regarding imaging modalities best suited for this purpose. We aim to review the current literature and perform a diagnostic meta-analysis comparing various imaging modalities that have been studied to differentiate tumor recurrence and RN. METHODS: A systematic search adherent to PRISMA guidelines was performed using Scopus, PubMed/MEDLINE, and Embase. Pooled sensitivities and specificities were determined using a random-effects or fixed-effects proportional meta-analysis based on heterogeneity. Using diagnostic odds ratios, a diagnostic frequentist random-effects network meta-analysis was performed, and studies were ranked using P-score hierarchical ranking. RESULTS: The analysis included 127 studies with a total of 220 imaging datasets, including the following imaging modalities: MRI (n = 10), MR Spectroscopy (MRS) (n = 28), dynamic contrast-enhanced MRI (n = 7), dynamic susceptibility contrast MRI (n = 36), MR arterial spin labeling (n = 5), diffusion-weighted imaging (n = 13), diffusion tensor imaging (DTI) (n = 2), PET (n = 89), and single photon emission computed tomography (SPECT) (n = 30). MRS had the highest pooled sensitivity (90.7%). DTI had the highest pooled specificity (90.5%). Our hierarchical ranking ranked SPECT and MRS as most preferable, and MRI was ranked as least preferable. CONCLUSION: These findings suggest SPECT and MRS carry greater utility than standard MRI in distinguishing RN from tumor recurrence.

Trends in Technology for Pedicle Screw Placement: A Temporal Meta-Analysis.

STUDY DESIGN: Systematic Review. OBJECTIVE: We sought to determine which method of the pedicle screw (PS) placement is most accurate and understand how the development of subsequent generations of robotic systems has changed placement accuracy over time. SUMMARY OF BACKGROUND DATA: Previous studies have demonstrated the success of robotic PS placement, but how this accuracy compares to other methods is unclear. METHODS: A systematic review following PRISMA Guidelines was performed on articles published between January 2000 and August 2021, comparing PS insertion methods with at least 10 screws per study arm. Single and multiple-arm trials were included. Data were extracted for patient outcomes, including optimal PS placement, misplacement, and accuracy. The logit-event rate of misplacement was calculated for each study. P values were adjusted for multiple comparisons using the Tukey post hoc correction. RESULTS: Our search revealed 127 studies, and 156 comparative arms, with 77,360 pedicle screws placed using five different modalities. Meta-regression of pooled accuracy revealed no significant changes in PS accuracy over time for freehand, 2D fluoroscopic navigation, 3D fluoroscopic navigation, and computed tomography navigation. Robotic navigation had a significant increase in accuracy over time ( P =0.036). Pooled misplacement rates were also compared across all modalities. Robotics was found to have the lowest rates of misplacement for PS compared to freehand ( P =0.0015) and 2D fluoroscopic navigation ( P =0.026). CONCLUSION: Our analysis is the largest study to date on pedicle screw placement. Pedicle screw placement through robotics was found to be superior due to its low misplacement rates compared with other modalities. Intraoperative 3D fluoroscopic navigation was found to have comparable misplacement rates. In addition, pedicle screw placement accuracy with robotics has continued to improve over time. This speaks to both the stability of the technology and the potential for continued improvement with new and more accurate robotic systems.

Disseminated blastomycosis with an intracranial fungoma in an immunocompetent patient: illustrative case.

BACKGROUND: Blastomyces dermatitidis is a fungus endemic to central and southern North America. While infection most commonly results in pneumonia, a small number of infections progress to systemic disease, which may include intracranial lesions. Progression to systemic disease is most common in immunocompromised patients, such as those with human immunodeficiency virus. OBSERVATIONS: The authors present a 44-year-old immunocompetent male who presented following a tonic-clonic seizure. Initial workup revealed a 19-mm enhancing intracranial mass. There was avid uptake of fluorescein sodium, and an en bloc resection of the mass was performed. Histopathology revealed B. dermatitidis. Medical management included amphotericin B and azole therapy. Postoperative recovery was uneventful, and no focal neurological deficits were appreciated. LESSONS: This case highlights the neurosurgical management of a rare intracranial fungal manifestation in an immunocompetent patient. A literature review was also performed to better understand the role of neurosurgery in fungal infections. There were limited cases of intracranial Blastomyces reported in immunocompetent patients, and neurosurgical management varied (no intervention, biopsy, resection) and was underreported. Too few cases are reported to suggest neurosurgical intervention for blastomycosis improves outcomes. Medical management was relatively standard with azole and amphotericin therapy.

Perioperative prophylaxis for surgical site infections in pediatric spinal surgery: a systematic review and network meta-analysis.

OBJECTIVE: Postoperative infections in pediatric spinal surgery commonly occur and necessitate reoperation(s). However, pediatric-specific infection prophylaxis guidelines are not available. This network meta-analysis compares perioperative prophylaxis methods including Betadine irrigation, saline irrigation, intrawound vancomycin powder, combination therapy (Betadine, vancomycin, gentamicin, and cefuroxime), Betadine irrigation plus vancomycin powder, and no intervention to determine the most efficacious prevention method. METHODS: A systematic review was performed by searching the PubMed, EBSCO, Scopus, and Web of Science databases for peer-reviewed articles published prior to February 2022 comparing two or more infection prophylaxis methods in patients younger than 22 years of age. Data were extracted for treatment modalities, patient demographics, and patient outcomes such as total number of infections, surgical site infections, deep infections, intraoperative blood loss, operative time, follow-up time, and postoperative complications. Quality and risk of bias was assessed using National Institutes of Health tools. A network meta-analysis was performed with reduction of infections as the primary outcome. RESULTS: Overall, 10 studies consisting of 5164 procedures were included. There was no significant difference between prophylactic treatment options in reduction of infection. However, three treatment options showed significant reduction in total infection compared with no prophylactic treatment: Betadine plus vancomycin (OR 0.22, 95% CI 0.09-0.54), vancomycin (OR 3.26, 95% CI 1.96-5.44), and a combination therapy (Betadine, vancomycin, gentamicin, and cefuroxime) (OR 0.24, 95% CI 0.07-0.75). P-Score hierarchical ranking estimated Betadine plus vancomycin to be the superior treatment to prevent total infections, deep infections, and surgical site infections (P-score 0.7876, 0.7175, and 0.7291, respectively). No prophylaxis treatment-related complications were reported. CONCLUSIONS: The results of this network meta-analysis show the strongest support for Betadine plus vancomycin as a method to reduce infections following pediatric spinal surgery. There was heterogeneity among studies and inconsistent outcome reporting; however, three effective treatment options are identified.

Geospatial evaluation of disparities in neurosurgical access in the United States.

When neurosurgical care is needed, the distance to a facility staffed with a neurosurgeon is critical. This work utilizes geospatial analysis to analyze access to neurosurgery in the Medicare population and relevant socioeconomic factors. Medicare billing and demographic data from 2015 to 2019 were combined with national National Provider Identifier (NPI) registry data to identify the average travel distance to reach a neurosurgeon as well as the number of neurosurgeons in each county. This was merged with U.S. Census data to capture 23 socioeconomic attributes. Moran's I statistic was calculated across counties. Socioeconomic variables were compared using ANOVA. Hotspots with the highest neurosurgeon access were predominantly located in the Mid-Atlantic region, central Texas, and southern Montana. Coldspots were found in the Great Plains, Midwest, and Southern Texas. There were statistically significant differences (p < 0.05) between high- and low-access counties, including: stroke prevalence, poverty, median household income, and total population density. There were no statistically significant differences in most races or ethnicities. Overall, there exist statistically significant clusters of decreased neurosurgery access within the United States, with varying sociodemographic characteristics between access hotspots and coldspots.

Anterior versus Posterior Ventricular Catheter Placement in Pediatric Patients: A Systematic Review and Meta-Analysis.

BACKGROUND: Ventriculoperitoneal shunt placement is the mainstay of treatment for hydrocephalus, but there are relatively high rates of malfunction. Shunt catheter entry can be performed anteriorly or posteriorly, with the body of evidence from randomized controlled trials and retrospective studies suggesting conflicting findings. METHODS: A systematic review of PubMed, Medline, Scopus, and Web of Science was performed adherent to PRISMA guidelines, searching for clinical studies examining outcomes for anterior or frontal and posterior or occipital ventriculoperitoneal shunt placement. A random-effects model meta-analysis was performed on R. RESULTS: Six studies (2 randomized controlled trials and 4 retrospective cohort studies) comprising 1808 patients were identified. There were no statistically significant differences between anterior and posterior ventriculoperitoneal shunt placement for the outcomes of poor catheter placement (odds ratio [OR], 0.74; P = 0.6) and shunt infections (OR, 1.01; P = 0.9). Posterior shunts trended toward greater number of shunt revisions (OR, 0.72; P = 0.06). Six and 12 months shunt survival was comparable between anterior and posterior approaches (P > 0.05). There were significant differences between long-term shunt survival (2 and 5 years shunt survival), favoring anterior shunt placement with greater odds of survival (OR, 1.91 and OR, 1.62, respectively; P < 0.05). CONCLUSIONS: We show that although anteriorly and posteriorly placed shunts have mostly comparable outcomes, shunt survival at 2-year and 5-year intervals favors anteriorly placed shunts. Additional well-designed clinical trials are needed to validate the findings of greater late shunt failure in posteriorly placed shunts, with more time-dependent statistical measures.

Endovascular and Medical Management of Cerebral Venous Thrombosis: A Systematic Review and Network Meta-Analysis.

OBJECTIVE: Management of cerebral venous thrombosis (CVT) involves minimizing expansion of the thrombus and promoting the recanalization of the venous sinus. While current guidelines include indications of endovascular management and anticoagulation with heparin and warfarin, the use of direct-acting oral anticoagulants (DOACs) has increased. In this study, we aim to conduct a network meta-analysis comparing these 3 therapeutic options: standard anticoagulation, DOACs, and endovascular treatments (EVTs). METHODS: Seventeen of 2265 studies identified from 4 publication databases met inclusion criteria for this network meta-analysis. Outcomes analyzed included modified Rankin Scale score, complications, mortality, and 6-month recanalization rates using a frequentist network meta-analysis approach. For each outcome, the preferential order of each intervention was ranked hierarchically based on P-score calculations used for frequentist network meta-analyses. RESULTS: Modified Rankin Scale outcomes were not significantly different based on the type of treatment modality (i.e., standard anticoagulation, DOACs, or EVT). Evaluation of complications demonstrated that patients treated with EVT were significantly more likely to experience a worse outcome than individuals treated with standard anticoagulation (odds ratio [OR] = 1.83, P = 0.04). Other comparisons did not demonstrate a significant difference in adverse events. For all-cause mortality outcomes, EVT demonstrated significantly greater odds of mortality than standard anticoagulation (OR = 1.89, P = 0.02). Mortality between DOACs and standard anticoagulation was not significantly different. When comparing 6-month recanalization rates, DOACs and EVT were significantly more effective than standard anticoagulation (OR = 1.93, OR = 2.2, P < 0.05). EVT followed by DOACs was preferred over standard anticoagulation for 6-month recanalization rates. CONCLUSIONS: This network meta-analysis evaluates the outcomes in CVT treatment, comparing standard anticoagulation, DOACs, and EVT, with evidence that DOACs have similar outcomes to standard anticoagulation in the treatment of CVT. EVT resulted in an increased risk of overall mortality but improved 6-month recanalization rates.

Ultra-High-Field MRI in the Diagnosis and Management of Gliomas: A Systematic Review.

Importance: Gliomas, tumors of the central nervous system, are classically diagnosed through invasive surgical biopsy and subsequent histopathological study. Innovations in ultra-high field (UHF) imaging, namely 7-Tesla magnetic resonance imaging (7T MRI) are advancing preoperative tumor grading, visualization of intratumoral structures, and appreciation of small brain structures and lesions. Objective: Summarize current innovative uses of UHF imaging techniques in glioma diagnostics and treatment. Methods: A systematic review in accordance with PRISMA guidelines was performed utilizing PubMed. Case reports and series, observational clinical trials, and randomized clinical trials written in English were included. After removing unrelated studies and those with non-human subjects, only those related to 7T MRI were independently reviewed and summarized for data extraction. Some preclinical animal models are briefly described to demonstrate future usages of ultra-high-field imaging. Results: We reviewed 46 studies (43 human and 3 animal models) which reported clinical usages of UHF MRI in the diagnosis and management of gliomas. Current literature generally supports greater resolution imaging from 7T compared to 1.5T or 3T MRI, improving visualization of cerebral microbleeds and white and gray matter, and providing more precise localization for radiotherapy targeting. Additionally, studies found that diffusion or susceptibility-weighted imaging techniques applied to 7T MRI, may be used to predict tumor grade, reveal intratumoral structures such as neovasculature and microstructures like axons, and indicate isocitrate dehydrogenase 1 mutation status in preoperative imaging. Similarly, newer imaging techniques such as magnetic resonance spectroscopy and chemical exchange saturation transfer imaging can be performed on 7T MRI to predict tumor grading and treatment efficacy. Geometrical distortion, a known challenge of 7T MRI, was at a tolerable level in all included studies. Conclusion: UHF imaging has the potential to preoperatively and non-invasively grade gliomas, provide precise therapy target areas, and visualize lesions not seen on conventional MRI.

Management of brain metastasis. Surgical resection versus stereotactic radiotherapy: a meta-analysis.

Background: Treatment of metastatic brain tumors often involves radiotherapy with or without surgical resection as the first step. However, the indications for when to use surgery are not clearly defined for certain tumor sizes and multiplicity. This study seeks to determine whether resection of brain metastases versus exclusive radiotherapy provided improved survival and local control in cases where metastases are limited in number and diameter. Methods: According to PRISMA guidelines, this meta-analysis compares outcomes from treatment of a median number of brain metastases ≤ 4 with a median diameter ≤ 4 cm with exclusive radiotherapy versus surgery followed by radiotherapy. Four randomized control trials and 11 observational studies (1693 patients) met inclusion criteria. For analysis, studies were grouped based on whether radiation involved stereotactic radiosurgery (SRS) or whole-brain radiotherapy (WBRT). Results: In both analyses, there was no difference in survival between surgery ± SRS versus SRS alone two years after treatment (OR 1.89 (95% CI: 0.47-7.55, P = .23) or surgery + WBRT versus radiotherapy alone (either WBRT and/or SRS) (OR 1.18 (95% CI: 0.76-1.84, P = .46). However, surgical patients demonstrated greater risk for local tumor recurrence compared to SRS alone (OR 2.20 (95% CI: 1.49-3.25, P < .0001)) and compared to WBRT/SRS (OR 2.93; 95% CI: 1.68-5.13, P = .0002). Conclusion: The higher incidence of local tumor recurrence for surgical patients suggests that more prospective studies are needed to clarify outcomes for treatment of 1-4 metastasis less than 4 cm diameter.

Comparison of fluorescein sodium, 5-ALA, and intraoperative MRI for resection of high-grade gliomas: A systematic review and network meta-analysis.

High grade gliomas (HGGs) are aggressive brain tumors associated with poor prognosis despite advances in surgical treatment and therapy. Navigated tumor resection has yielded improved outcomes for patients. We compare 5-ALA, fluorescein sodium (FS), and intraoperative MRI (IMRI) with no image guidance to determine the best intraoperative navigation method to maximize rates of gross total resection (GTR) and outcomes. A frequentist network meta-analysis was performed following standard PRISMA guidelines (PROSPERO registration CRD42021268659). Surface-under-the-cumulative ranking (SUCRA) analysis was executed to hierarchically rank modalities by the outcomes of interest. Heterogeneity was measured by the I2 statistic. Publication bias was assessed by funnel plots and the use of Egger's test. Statistical significance was determined by p < 0.05. Twenty-three studies were included for analysis with a total of 2,643 patients. Network meta-analysis comparing 5-ALA, IMRI, and FS was performed. The primary outcome assessed was the rate of GTR. Analysis revealed the superiority of all intraoperative navigation to control (no navigation). SUCRA analysis revealed the superiority of IMRI + 5-ALA, IMRI alone, followed by FS, and 5-ALA. Overall survival (OS) and progression free survival (PFS) were also examined. FS (vs. control) was associated with improved OS, while IMRI was associated with improved PFS (vs. control, FS, and 5-ALA). Intraoperative navigation using IMRI, FS, and 5-ALA lead to greater rates of GTR in HGGs. FS and 5-ALA also yielded improvement in OS and PFS. Further studies are needed to evaluate differences in survival benefit, operative duration, and cost.

Robotic external ventricular drain placement for acute neurosurgical care in low-resource settings: feasibility considerations and a prototype design.

OBJECTIVE: Emergency neurosurgical care in lower-middle-income countries faces pronounced shortages in neurosurgical personnel and infrastructure. In instances of traumatic brain injury (TBI), hydrocephalus, and subarachnoid hemorrhage, the timely placement of external ventricular drains (EVDs) strongly dictates prognosis and can provide necessary stabilization before transfer to a higher-level center of care that has access to neurosurgery. Accordingly, the authors have developed an inexpensive and portable robotic navigation tool to allow surgeons who do not have explicit neurosurgical training to place EVDs. In this article, the authors aimed to highlight income disparities in neurosurgical care, evaluate access to CT imaging around the world, and introduce a novel, inexpensive robotic navigation tool for EVD placement. METHODS: By combining the worldwide distribution of neurosurgeons, CT scanners, and gross domestic product with the incidence of TBI, meningitis, and hydrocephalus, the authors identified regions and countries where development of an inexpensive, passive robotic navigation system would be most beneficial and feasible. A prototype of the robotic navigation system was constructed using encoders, 3D-printed components, machined parts, and a printed circuit board. RESULTS: Global analysis showed Montenegro, Antigua and Barbuda, and Seychelles to be primary candidates for implementation and feasibility testing of the novel robotic navigation system. To validate the feasibility of the system for further development, its performance was analyzed through an accuracy study resulting in accuracy and repeatability within 1.53 ± 2.50 mm (mean ± 2 × SD, 95% CI). CONCLUSIONS: By considering regions of the world that have a shortage of neurosurgeons and a high incidence of EVD placement, the authors were able to provide an analysis of where to prioritize the development of a robotic navigation system. Subsequently, a proof-of-principle prototype has been provided, with sufficient accuracy to target the ventricles for EVD placement.

Evaluating robotic pedicle screw placement against conventional modalities: a systematic review and network meta-analysis.

OBJECTIVE: Several approaches have been studied for internal fixation of the spine using pedicle screws (PSs), including CT navigation, 2D and 3D fluoroscopy, freehand, and robotic assistance. Robot-assisted PS placement has been controversial because training requirements, cost, and previously unclear benefits. This meta-analysis compares screw placement accuracy, operative time, intraoperative blood loss, and overall complications of PS insertion using traditional freehand, navigated, and robot-assisted methods. METHODS: A systematic review was performed of peer-reviewed articles indexed in several databases between January 2000 and August 2021 comparing ≥ 2 PS insertion methods with ≥ 10 screws per treatment arm. Data were extracted for patient outcomes, including PS placement, misplacement, and accuracy; operative time, overall complications, intraoperative blood loss, postoperative hospital length of stay, postoperative Oswestry Disability Index (ODI) score, and postoperative visual analog scale (VAS) score for back pain. Risk of bias was assessed using the Newcastle-Ottawa score and Cochrane tool. A network meta-analysis (NMA) was performed to estimate PS placement accuracy as the primary outcome. RESULTS: Overall, 78 studies consisting of 6262 patients and > 31,909 PSs were included. NMA results showed that robot-assisted and 3D-fluoroscopy PS insertion had the greatest accuracy compared with freehand (p < 0.01 and p < 0.001, respectively), CT navigation (p = 0.02 and p = 0.04, respectively), and 2D fluoroscopy (p < 0.01 and p < 0.01, respectively). The surface under the cumulative ranking (SUCRA) curve method further demonstrated that robot-assisted PS insertion accuracy was superior (S = 0.937). Optimal screw placement was greatest in robot-assisted (S = 0.995) placement, and misplacement was greatest with freehand (S = 0.069) approaches. Robot-assisted placement was favorable for minimizing complications (S = 0.876), while freehand placement had greater odds of complication than robot-assisted (OR 2.49, p < 0.01) and CT-navigation (OR 2.15, p = 0.03) placement. CONCLUSIONS: The results of this NMA suggest that robot-assisted PS insertion has advantages, including improved accuracy, optimal placement, and minimized surgical complications, compared with other PS insertion methods. Limitations included overgeneralization of categories and time-dependent effects.