Pilot trial of perampanel on peritumoral hyperexcitability and clinical outcomes in newly diagnosed high-grade glioma.

Background: Glutamatergic neuron-glioma synaptogenesis and peritumoral hyperexcitability promote glioma growth in a positive feedback loop. The objective of this study was to evaluate the feasibility and estimated effect sizes of the AMPA-R antagonist, perampanel, on intraoperative electrophysiologic hyperexcitability and clinical outcomes. Methods: An open-label trial was performed comparing perampanel to standard of care (SOC) in patients undergoing resection of newly-diagnosed radiologic high-grade glioma. Perampanel was administered as a pre-operative loading dose followed by maintenance therapy until progressive disease or up to 12-months. SOC treatment involved levetiracetam for 7-days or as clinically indicated. The primary outcome of hyperexcitability was defined by intra-operative electrocorticography high frequency oscillation (HFO) rates. Seizure-freedom and overall survival (OS) were estimated by the Kaplan-Meier method. Tissue concentrations of perampanel, levetiracetam, and metabolites were measured by mass spectrometry. Results: HFO rates were similar between perampanel-treated and SOC cohorts. The trial was terminated early after interim analysis for futility, and outcomes assessed in 11 patients (7 perampanel-treated, 4 SOC). Over a median 281 days of post-enrollment follow-up, 27% of patients had seizures, including 14% treated with perampanel and 50% treated with SOC. OS in perampanel-treated patients was similar to a glioblastoma reference cohort (p=0.81). Glutamate concentrations in surface biopsies were positively correlated with HFO rates in adjacent electrode contacts and were not significantly associated with treatment assignment or drug concentrations. Conclusions: A peri-operative loading regimen of perampanel was safe and well-tolerated, with similar peritumoral hyperexcitability as in levetiracetam-treated patients. Maintenance anti-glutamatergic therapy was not observed to impact survival outcomes.

Surgical Navigation in the Anterior Skull Base Using 3-Dimensional Endoscopy and Surface Reconstruction.

Importance: Image guidance is an important adjunct for endoscopic sinus and skull base surgery. However, current systems require bulky external tracking equipment, and their use can interrupt efficient surgical workflow. Objective: To evaluate a trackerless surgical navigation system using 3-dimensional (3D) endoscopy and simultaneous localization and mapping (SLAM) algorithms in the anterior skull base. Design, Setting, and Participants: This interventional deceased donor cohort study and retrospective clinical case study was conducted at a tertiary academic medical center with human deceased donor specimens and a patient with anterior skull base pathology. Exposures: Participants underwent endoscopic endonasal transsphenoidal dissection and surface model reconstruction from stereoscopic video with registration to volumetric models segmented from computed tomography (CT) and magnetic resonance imaging. Main Outcomes and Measures: To assess the fidelity of surface model reconstruction and accuracy of surgical navigation and surface-CT model coregistration, 3 metrics were calculated: reconstruction error, registration error, and localization error. Results: In deceased donor models (n = 9), high-fidelity surface models of the posterior wall of the sphenoid sinus were reconstructed from stereoscopic video and coregistered to corresponding volumetric CT models. The mean (SD; range) reconstruction, registration, and localization errors were 0.60 (0.24; 0.36-0.93), 1.11 (0.49; 0.71-1.56) and 1.01 (0.17; 0.78-1.25) mm, respectively. In a clinical case study of a patient who underwent a 3D endoscopic endonasal transsphenoidal resection of a tubercular meningioma, a high-fidelity surface model of the posterior wall of the sphenoid was reconstructed from intraoperative stereoscopic video and coregistered to a volumetric preoperative fused CT magnetic resonance imaging model with a root-mean-square error of 1.38 mm. Conclusions and Relevance: The results of this study suggest that SLAM algorithm-based endoscopic endonasal surgery navigation is a novel, accurate, and trackerless approach to surgical navigation that uses 3D endoscopy and SLAM-based algorithms in lieu of conventional optical or electromagnetic tracking. While multiple challenges remain before clinical readiness, a SLAM algorithm-based endoscopic endonasal surgery navigation system has the potential to improve surgical efficiency, economy of motion, and safety.

Empty sella in somatotropic pituitary adenomas; a series of 23 cases.

Purpose: We aimed to investigate empty sella syndrome in somatotrophic pituitary adenoma for possible etiology, complications, and treatment options. Method: Among over 2,000 skull base masses that have been managed in our center since 2013, we searched for growth hormone-producing adenomas. Clinical, surgical, and imaging data were retrospectively collected from hospital records to check for sella that lacked pituitary tissue on routine imaging. Result: In 220 somatotrophic adenomas, 23 patients had an empty sella with surgical and follow-up data. The mean age of the sample was 46 years with the same male-to-female ratio. Five cases had partial empty sella and the rest were complete empty sellas. The most common simultaneous hormonal disturbance was high prolactin levels. Six had adenoma invasion into the clivus or sphenoid sinus and 10 had cavernous sinus intrusion. Peri-operative low-flow and high-flow cerebrospinal fluid (CSF) leaks were encountered in one and two patients, respectively, which were successfully sealed by abdominal fat. The majority of cases required growth hormone replacement therapy while it was controlled without any replacement therapy in nine patients. No pituitary hormonal disturbance occurred after transsphenoidal surgery except for hypothyroidism in one patient. Conclusion: An empty sella filled with fluid can be detected frequently in pituitary adenomas, especially in the setting of acromegaly. The pituitary gland may be pushed to the roof of the sella and might be visible as a narrow rim on imaging or may be detected in unusual places out of the sella. The pathophysiology behind such finding originates from soft and hard tissue changes and CSF pressure alternations during abundant growth hormone production.

Elevated risk of recurrence and retreatment for silent pituitary adenomas.

PURPOSE: Pituitary adenomas are the most common tumor of the pituitary gland and comprise nearly 15% of all intracranial masses. These tumors are stratified into functional or silent categories based on their pattern of hormone expression and secretion. Preliminary evidence supports differential clinical outcomes between some functional pituitary adenoma (FPA) subtypes and silent pituitary adenoma (SPA) subtypes. METHODS: We collected and analyzed the medical records of all patients undergoing resection of SPAs or FPAs from a single high-volume neurosurgeon between 2007 and 2018 at Brigham and Women's Hospital. Descriptive statistics and the Mantel-Cox log-rank test were used to identify differences in outcomes between these cohorts, and multivariate logistic regression was used to identify predictors of radiographic recurrence for SPAs. RESULTS: Our cohort included 88 SPAs and 200 FPAs. The majority of patients in both cohorts were female (48.9% of SPAs and 63.5% of FPAs). SPAs were larger in median diameter than FPAs (2.1 cm vs. 1.2 cm, p < 0.001). The most frequent subtypes of SPA were gonadotrophs (55.7%) and corticotrophs (30.7%). Gross total resection (GTR) was achieved in 70.1% of SPA resections and 86.0% of FPA resections (p < 0.001). SPAs had a higher likelihood of recurring (hazard ratio [HR] 3.2, 95% confidence interval [95%CI] 1.6-7.2) and a higher likelihood of requiring retreatment for recurrence (HR 2.5; 95%CI 1.0-6.1). Subset analyses revealed that recurrence and retreatment were more both likely for subtotally resected SPAs than subtotally resected FPAs, but this pattern was not observed in SPAs and FPAs after GTR. Among SPAs, recurrence was associated with STR (odds ratio [OR] 9.3; 95%CI 1.4-64.0) and younger age (OR 0.92 per year; 95%CI 0.88-0.98) in multivariable analysis. Of SPAs that recurred, 12 of 19 (63.2%) were retreated with repeat surgery (n = 11) or radiosurgery (n = 1), while the remainder were observed (n = 7).There were similar rates of recurrence across different SPA subtypes. CONCLUSION: Patients undergoing resection of SPAs should be closely monitored for disease recurrence through more frequent clinical follow-up and diagnostic imaging than other adenomas, particularly among patients with STR and younger patients. Several patients can be observed after radiographic recurrence, and the decision to retreat should be individualized. Longitudinal clinical follow-up of SPAs, including an assessment of symptoms, endocrine function, and imaging remains critical.

Evaluating the Utility of Repeat Computed Tomography Scans in Patients with Isolated Mild Traumatic Subarachnoid Hemorrhage.

BACKGROUND: Traumatic subarachnoid hemorrhage (tSAH) is a common consequence of head trauma. Treatment of patients with tSAH commonly involves serial computed tomography (CT) scans to assess for expansile hemorrhage. However, growing evidence suggests that these patients rarely deteriorate or require neurosurgical intervention. We assessed the utility of repeat CT scans in adult patients with isolated tSAH and an intact initial neurological examination. METHODS: Patients presenting to Mass General Brigham hospitals with tSAH between 2000 and 2021 were eligible for inclusion in this retrospective cohort study. Patients were excluded if subarachnoid hemorrhage was nontraumatic, they experienced another form of intracerebral hemorrhage, or they had a documented Glasgow Coma Scale score of ≤12 and/or poor presenting neurological examination. Univariate and multivariate regression models were used for statistical analysis. RESULTS: Overall, 405 patients were included (191 male). The most common mechanism of trauma was fall from standing (58%). The mean number of total CT scans for all patients was 2.3, with 329 patients (80%) receiving ≥2 scans. In 309 patients, no significant neurological symptoms were present. No patients developed acute neurological deterioration or required neurosurgical intervention related to their bleed, although 5 patients had mild hemorrhagic expansion on follow-up imaging. CONCLUSIONS: In this study, repeat imaging rarely demonstrated meaningful hemorrhagic expansion in this cohort of neurologically intact patients with isolated tSAH. In these patients with mild traumatic brain injury, excessive CT scans are perhaps unlikely to affect patient management and may present unnecessary burden to patients and hospital systems.

Influences of compound age and identity in the effectiveness of insect quinone secretions against the fungus Beauveria bassiana.

Chemical defences against parasites and pathogens can be seen in a wide range of animal taxa, including insect pests such as the red flour beetle Tribolium castaneum. Antimicrobial quinone-based secretions can be used by these beetles to defend against various parasites, particularly the fungal entomopathogen Beauveria bassiana. While quinone secretions can inhibit B. bassiana growth, it is unknown how long they remain effective or how individual secretion compounds contribute to growth inhibition. Here, we tested each individual component of the quinone secretions (methyl-1,4-benzoquinone, ethyl-1,4-benzoquinone, and 1-pentadecene), as well as two mixed solutions that represent the composition range found in natural T. castaneum secretions, after aging for 0, 24, or 72 h. The two quinone compounds equally contributed to B. bassiana inhibition, but their efficacy was significantly reduced after 24 h, with no growth inhibition after 72 h. This indicates that quinones protect insects against B. bassiana for only a limited time, perhaps requiring constant secretion into the environment to effectively defend against this fungal threat. Future investigations may consider the extent to which quinone secretions are effective against other parasites, as well as how their ability to cause parasite damage changes with compound age.

Intrasellar Arachnoid Diverticulae as a Risk Factor for Intraoperative Cerebrospinal Fluid Leakage in Patients Undergoing Endoscopic Transsphenoidal Surgery.

BACKGROUND AND OBJECTIVES: Intrasellar arachnoid diverticulae can often be identified on preoperative imaging in patients undergoing endoscopic transsphenoidal surgery. The objective of this study was to characterize arachnoid diverticulae both qualitatively and quantitatively in a large institutional cohort of patients with pituitary tumors and to evaluate its association with intraoperative cerebrospinal fluid (CSF) leak. METHODS: Preoperative imaging studies of 530 patients who underwent primary endoscopic transsphenoidal resection of pituitary tumors were examined both quantitatively and qualitatively for the presence of an intrasellar arachnoid diverticulum. A matched cohort analysis was performed to compare patients with a "significant" (>50% sellar depth) diverticulum with those with nonsignificant/no diverticulum. Morphologically, diverticulae were separately classified as Type 1 (ventral CSF cleft with no tumor/gland tissue between sellar face and infundibulum) or Type 2 (central CSF cleft with tumor/gland tissue between sellar face and infundibulum). RESULTS: Arachnoid diverticulae were noted in 40.2% of cases, and diverticulum depth was linearly correlated with tumor size and body mass index. A significant diverticulum was identified in 66 cases (12.5%) and was significantly associated with the functional tumor subtype (P = .005) and intraoperative CSF leak (P < .001). Type 1 clefts were associated with nonfunctional pathology (P = .034) and the presence of suprasellar extension (P = .035) and tended to be deeper than Type 2 clefts (P < .001), with a higher incidence of intraoperative CSF leak (P = .093). On logistic regression analysis, only the presence of a significant diverticulum was independently associated with intraoperative CSF leak (odds ratio 4.545; 95% CI 2.418-8.544; P < .001). CONCLUSION: The presence of an intrasellar arachnoid diverticulum should alert the surgeon to an elevated risk of intraoperative CSF leak during transsphenoidal surgery for pituitary tumors. A relatively limited surgical exposure tailored to the craniocaudal extent of the sellar pathology should be considered in these patients.

The role of surgical management for prolactin-secreting tumors in the era of dopaminergic agonists: An international multicenter report.

OBJECTIVE: First-line prolactin-secreting tumor (PST) management typically involves treatment with dopamine agonists and the role of surgery remains to be further explored. We examined the international experience of 12 neurosurgical centers to assess the patient characteristics, safety profile, and effectiveness of surgery for PST management. METHODS: Patients surgically treated for PST from January 2017 through December 2020 were evaluated for surgical characteristics, outcomes, and safety. RESULTS: Among 272 patients identified (65.1% female), the mean age was 38.0 ± 14.3 years. Overall, 54.4% of PST were macroadenomas. Minor complications were seen in 39.3% of patients and major complications were in 4.4%. The most common major complications were epistaxis and worsened vision. Most minor complications involved electrolyte/sodium dysregulation. At 3-6 months, local control on imaging was achieved in 94.8% of cases and residual/recurrent tumor was seen in 19.3%. Reoperations were required for 2.9% of cases. On multivariate analysis, previous surgery was significantly predictive of intraoperative complications (6.14 OR, p < 0.01) and major complications (14.12 OR, p < 0.01). Previous pharmacotherapy (0.27 OR, p = 0.02) and cavernous sinus invasion (0.19 OR, p = 0.03) were significantly protective against early endocrinological cure. Knosp classification was highly predictive of residual tumor or PST recurrence on 6-month follow-up imaging (4.60 OR, p < 0.01). There was noted institutional variation in clinical factors and outcomes. CONCLUSION: Our results evaluate a modern, multicenter, global series of PST. These data can serve as a benchmark to compare with DA therapy and other surgical series. Further study and longer term outcomes could provide insight into how patients benefit from surgical treatment.

The Global Macroeconomic Burden of Burn Injuries.

BACKGROUND: Standardized estimates of global economic losses from burn injuries are lacking. The primary objective of this study was to determine the global macroeconomic consequences of burn injuries and their geographic distribution. METHODS: Using the Institute of Health Metrics and Evaluation database (2009 and 2019), mean and 95% uncertainty interval (UI) data on incidence, mortality, and disability-adjusted life-years (DALYs) from injuries caused by fire, heat, and hot substances were collected. Gross domestic product (GDP) data were analyzed together with DALYs to estimate macroeconomic losses globally using a value of lost welfare approach. RESULTS: There were 9 million global burn cases (95% UI, 6.8 to 11.2 million) and 111,000 deaths from burns (95% UI, 88,000 to 132,000 deaths) in 2019, representing a total of 7.5 million DALYs (95% UI, 5.8 to 9.5 million DALYs). This represented welfare losses of $112 billion (95% UI, $78 to $161 billion), or 0.09% of GDP (95% UI, 0.06% to 0.13%). Welfare losses as a share of GDP were highest in low- and middle-income countries (LMICs) of Oceania (0.24%; 95% UI, 0.09% to 0.42%) and Eastern Europe (0.24%; 95% UI, 0.19% to 0.30%) compared with high-income country regions such as Western Europe (0.06%; 95% UI, 0.04% to 0.09%). Mortality-incidence ratios were highest in LMIC regions, highlighting a lack of treatment access, with southern sub-Saharan Africa reporting a mortality-incidence ratio of 40.1 per 1000 people compared with 1.9 for Australasia. CONCLUSIONS: Burden of disease and resulting economic losses because of burn injuries are substantial worldwide and are disproportionately higher in LMICs. Possible effective solutions include targeted education, advocacy, and legislation to decrease incidence and investing in existing burn centers to improve treatment access.

Dexamethasone and overall survival and progression free survival in patients with newly diagnosed glioblastoma: a meta-analysis.

PURPOSE: Glioblastomas, the most common primary malignant brain tumors in adults, still hold poor prognosis. Corticosteroids, such as dexamethasone, are usually prescribed to reduce peritumoral edema and limit neurological symptoms, although potential detrimental effects of these drugs have been described. The present meta-analysis aimed to explore the association of dexamethasone with overall survival (OS) and progression free survival (PFS) in patients with newly diagnosed glioblastoma. METHODS: PubMed, Cochrane Library, Embase, and ClinicalTrials.gov were searched for pertinent studies following the Preferred Reporting Items of Systematic Review and Meta-Analysis checklist. Pooled multivariable-adjusted hazard ratios (HR) for OS and PFS and their associated 95% confidence intervals (CIs) were calculated using the random-effects model and the heterogeneity among studies was assessed using I2. The quality of evidence was assessed using the GRADE criteria. RESULTS: Seven studies were included, pooling data of 1,257 patients, with age varying from 11 to 81 years. Glioblastoma patients on pre- or peri-operative dexamethasone were associated with a significantly poorer overall survival (HR: 1.33, 95% CI: 1.15, 1.55; 7 studies; I2: 59.9%) and progression free survival (HR: 1.77, 95% CI: 1.05, 2.97; 3 studies; I2: 71.1%) compared to patients not on dexamethasone. The quality of evidence was moderate for overall survival and low for progression free survival. CONCLUSION: Dexamethasone appeared to be associated with poor survival outcomes of glioblastoma patients.

Morphological Classification of Pituitary Tumors With Suprasellar Extension.

BACKGROUND AND OBJECTIVES: The objective of this study was to study the association among various morphological parameters and surgical outcomes in pituitary macroadenomas with suprasellar extension. METHODS: MRI studies of 160 patients undergoing endoscopic transsphenoidal resection of pituitary macroadenomas with suprasellar extension were reviewed. In the coronal plane, tumors were classified into Type 1 (dome-shaped, no constriction at the level of diaphragma sellae) and Type 2 (dumbbell-shaped, with constriction at the level of diaphragma sellae). Based on the dome-to-neck ratio (D/Nr), Type 2 tumors were further classified as Type 2A (wide neck; D/Nr >1 and <1.3) and Type 2B (narrow neck; D/Nr ≥1.3). Surgical outcomes and complications were analyzed using a logistic regression model. Overall extent of resection (EOR) and presence of residual sellar-suprasellar tumor was separately assessed in all patients with available postoperative MRI (n = 149). RESULTS: There were 108 Type 1 tumors and 26 patients each in the Type 2A and Type 2B subgroups. Tumor subtype was significantly associated with tumor size (P < .001), intraoperative cerebrospinal fluid leak (P < .001), EOR (P < .001), postoperative suprasellar residual tumor (P < .001), and postoperative complications, including diabetes insipidus (P = .005) and visual worsening (P = .003). On multivariate analysis, after adjusting for confounders, Type 2B tumors were negatively associated with EOR (odds ratio [OR] 0.22; 95% CI 0.07-0.68; P = .008) and associated with the presence of postoperative suprasellar residual tumor (OR 18.08; 95% CI 5.20-62.89; P < .001), intraoperative cerebrospinal fluid leak (OR 5.33; 95% CI 1.89-14.99; P = .002), and postoperative diabetes insipidus (OR 4.89; 95% CI 1.67-14.35; P < .001). CONCLUSION: Preoperative tumor classification based on D/Nr is clinically and surgically relevant, and Type 2B macroadenomas are significantly associated with lower rates of gross total resection and higher rates of postoperative complications after endoscopic transsphenoidal resection.

Aerobic exercise interventions to address impaired quality of life in patients with pituitary tumors.

Patients with pituitary tumors may experience persistent fatigue and reduced physical activity, based on subjective measures after treatment. These symptoms may persist despite gross total resection of their tumors and biochemical normalization of pituitary function. While reduced quality of life has been commonly acknowledged in pituitary tumor patients, there is a lack of studies on what interventions may be best implemented to ameliorate these issues, particularly when hormonal levels have otherwise normalized. Aerobic exercise programs have been previously described to ameliorate symptoms of chronic fatigue and reduced physical capacity across a variety of pathologies in the literature. As such, a prescribed aerobic exercise program may be an underrecognized but potentially impactful intervention to address quality of life in pituitary tumor patients. This review seeks to summarize the existing literature on aerobic exercise interventions in patients with pituitary tumors. In addition, future areas of study are discussed, including tailoring exercise programs to the hormonal status of the patient and incorporating more objective measures in monitoring response to interventions.

Positioning SUMO as an immunological facilitator of oncolytic viruses for high-grade glioma.

Oncolytic viral (OV) therapies are promising novel treatment modalities for cancers refractory to conventional treatment, such as glioblastoma, within the central nervous system (CNS). Although OVs have received regulatory approval for use in the CNS, efficacy is hampered by obstacles related to delivery, under-/over-active immune responses, and the "immune-cold" nature of most CNS malignancies. SUMO, the Small Ubiquitin-like Modifier, is a family of proteins that serve as a high-level regulator of a large variety of key physiologic processes including the host immune response. The SUMO pathway has also been implicated in the pathogenesis of both wild-type viruses and CNS malignancies. As such, the intersection of OV biology with the SUMO pathway makes SUMOtherapeutics particularly interesting as adjuvant therapies for the enhancement of OV efficacy alone and in concert with other immunotherapeutic agents. Accordingly, the authors herein provide: 1) an overview of the SUMO pathway and its role in CNS malignancies; 2) describe the current state of CNS-targeted OVs; and 3) describe the interplay between the SUMO pathway and the viral lifecycle and host immune response.

Crooke Cell Adenoma Confers Poorer Endocrinological Outcomes Compared with Corticotroph Adenoma: Results of a Multicenter, International Analysis.

BACKGROUND: Crooke cell adenomas (CCAs) are a rare, aggressive subset of secretory pituitary corticotroph adenomas (sCTAs) found in 5%-10% of patients with Cushing disease. Multiple studies support worse outcomes in CCAs but are limited by small sample size and single-institution databases. We compared outcomes in CCA and sCTA using a multicenter, international retrospective database of high-volume skull base centers. METHODS: Patients surgically treated for pituitary adenoma from January 2017 through December 2020 were included. RESULTS: Among 2826 patients from 12 international centers, 20 patients with CCA and 480 patients with sCTA were identified. No difference in baseline demographics, tumor characteristics, or postoperative complications was seen. Microsurgical approaches (60% CCA vs. 62.3% sCTA) were most common. Gross total resection was higher in CCA patients (100% vs. 83%, P = 0.05). Among patients with gross total resection according to intraoperative findings, fewer CCA patients had postoperative hormone normalization of pituitary function (50% vs. 77.8%, P < 0.01) and remission of hypersecretion by 3-6 months (75% vs. 84.3%, P < 0.01). This was the case despite CCA having better local control rates (100% vs. 96%, P < 0.01) and fewer patients with remnant on magnetic resonance imaging (0% vs. 7.2%, P < 0.01). A systematic literature review of 35 studies reporting on various treatment strategies reiterated the high rate of residual tumor, persistent hypercortisolism, and tumor-related mortality in CCA patients. CONCLUSIONS: This modern, multicenter series of patients with CCA reflects their poor prognosis and reduced postsurgical hormonal normalization. Further work is necessary to better understand the pathophysiology of CCA to devise more targeted treatment approaches.

FDA-approved machine learning algorithms in neuroradiology: A systematic review of the current evidence for approval.

Over the past decade, machine learning (ML) and artificial intelligence (AI) have become increasingly prevalent in the medical field. In the United States, the Food and Drug Administration (FDA) is responsible for regulating AI algorithms as "medical devices" to ensure patient safety. However, recent work has shown that the FDA approval process may be deficient. In this study, we evaluate the evidence supporting FDA-approved neuroalgorithms, the subset of machine learning algorithms with applications in the central nervous system (CNS), through a systematic review of the primary literature. Articles covering the 53 FDA-approved algorithms with applications in the CNS published in PubMed, EMBASE, Google Scholar and Scopus between database inception and January 25, 2022 were queried. Initial searches identified 1505 studies, of which 92 articles met the criteria for extraction and inclusion. Studies were identified for 26 of the 53 neuroalgorithms, of which 10 algorithms had only a single peer-reviewed publication. Performance metrics were available for 15 algorithms, external validation studies were available for 24 algorithms, and studies exploring the use of algorithms in clinical practice were available for 7 algorithms. Papers studying the clinical utility of these algorithms focused on three domains: workflow efficiency, cost savings, and clinical outcomes. Our analysis suggests that there is a meaningful gap between the FDA approval of machine learning algorithms and their clinical utilization. There appears to be room for process improvement by implementation of the following recommendations: the provision of compelling evidence that algorithms perform as intended, mandating minimum sample sizes, reporting of a predefined set of performance metrics for all algorithms and clinical application of algorithms prior to widespread use. This work will serve as a baseline for future research into the ideal regulatory framework for AI applications worldwide.

Defining benchmark outcomes for transsphenoidal surgery of pituitary adenomas: a multicenter analysis.

IMPORTANCE: Benchmarks aid in improve outcomes for surgical procedures. However, best achievable results that have been validated internationally for transsphenoidal surgery (TS) are not available. OBJECTIVE: We aimed to establish standardized outcome benchmarks for TS of pituitary adenomas. DESIGN: A total of 2685 transsphenoidal tumor resections from 9 expert centers in 3 continents were analyzed. SETTING: Patients were risk stratified, and the median values of each center's outcomes were established. The benchmark was defined as the 75th percentile of all median values for a particular outcome. The postoperative benchmark outcomes included surgical factors, endocrinology-specific values, and neurology-specific values. RESULTS: Of 2685 patients, 1149 (42.8%) defined the low-risk benchmark cohort. Within these benchmark cases, 831 (72.3%) patients underwent microscopic TS, and 308 (26.8%) patients underwent endoscopic endonasal resection. Of all tumors, 799 (29.8%) cases invaded the cavernous sinus. The postoperative complication rate was 19.6% with mortality between 0.0% and 0.8%. Benchmark cutoffs were ≤2.9% for reoperation rate, ≤1.9% for cerebrospinal fluid leak requiring intervention, and ≤15.5% for transient diabetes insipidus. At 6 months, benchmark cutoffs were calculated as follows: readmission rate: ≤6.9%, new hypopituitarism ≤6.0%, and tumor remnant ≤19.2%. CONCLUSIONS: This analysis defines benchmark values for TS targeting morbidity and mortality and represents the best outcomes in the best patients in expert centers. These cutoffs can be used to assess different centers, patient populations, and novel surgical techniques. It should be noted that the benchmark values may influence each other and must be evaluated in their own context.

Traditional Machine Learning Methods versus Deep Learning for Meningioma Classification, Grading, Outcome Prediction, and Segmentation: A Systematic Review and Meta-Analysis.

BACKGROUND: Meningiomas are common intracranial tumors. Machine learning (ML) algorithms are emerging to improve accuracy in 4 primary domains: classification, grading, outcome prediction, and segmentation. Such algorithms include both traditional approaches that rely on hand-crafted features and deep learning (DL) techniques that utilize automatic feature extraction. The aim of this study was to evaluate the performance of published traditional ML versus DL algorithms in classification, grading, outcome prediction, and segmentation of meningiomas. METHODS: A systematic review and meta-analysis were conducted. Major databases were searched through September 2021 for publications evaluating traditional ML versus DL models on meningioma management. Performance measures including pooled sensitivity, specificity, F1-score, area under the receiver-operating characteristic curve, positive and negative likelihood ratios (LR+, LR-) along with their respective 95% confidence intervals (95% CIs) were derived using random-effects models. RESULTS: Five hundred thirty-four records were screened, and 43 articles were included, regarding classification (3 articles), grading (29), outcome prediction (7), and segmentation (6) of meningiomas. Of the 29 studies that reported on grading, 10 could be meta-analyzed with 2 DL models (sensitivity 0.89, 95% CI: 0.74-0.96; specificity 0.91, 95% CI: 0.45-0.99; LR+ 10.1, 95% CI: 1.33-137; LR- 0.12, 95% CI: 0.04-0.59) and 8 traditional ML (sensitivity 0.74, 95% CI: 0.62-0.83; specificity 0.93, 95% CI: 0.79-0.98; LR+ 10.5, 95% CI: 2.91-39.5; and LR- 0.28, 95% CI: 0.17-0.49). The insufficient performance metrics reported precluded further statistical analysis of other performance metrics. CONCLUSIONS: ML on meningiomas is mostly carried out with traditional methods. For meningioma grading, traditional ML methods generally had a higher LR+, while DL models a lower LR-.

Micro RNAs as a Diagnostic Marker between Glioma and Primary CNS Lymphoma: A Systematic Review.

Differentiating glioma from primary central nervous system lymphoma (PCNSL) can be challenging, and current diagnostic measures such as MRI and biopsy are of limited efficacy. Liquid biopsies, which detect circulating biomarkers such as microRNAs (miRs), may provide valuable insights into diagnostic biomarkers for improved discrimination. This review aimed to investigate the role of specific miRs in diagnosing and differentiating glioma from PCNSL. A systematic search was conducted of PubMed, Scopus, Web of Science, and Embase for articles on liquid biopsies as a diagnostic method for glioma and PCNSL. Sixteen dysregulated miRs were identified with significantly different levels in glioma and PCNSL, including miR-21, which was the most prominent miR with higher levels in PCNSL, followed by glioma, including glioblastoma (GBM), and control groups. The lowest levels of miR-16 and miR-205 were observed in glioma, followed by PCNSL and control groups, whereas miR-15b and miR-301 were higher in both tumor groups, with the highest levels observed in glioma patients. The levels of miR-711 were higher in glioma (including GBM) and downregulated in PCNSL compared to the control group. This review suggests that using these six circulating microRNAs as liquid biomarkers with unique changing patterns could aid in better discrimination between glioma, especially GBM, and PCNSL.

Artificial Intelligence in Neurosurgery: A State-of-the-Art Review from Past to Future.

In recent years, there has been a significant surge in discussions surrounding artificial intelligence (AI), along with a corresponding increase in its practical applications in various facets of everyday life, including the medical industry. Notably, even in the highly specialized realm of neurosurgery, AI has been utilized for differential diagnosis, pre-operative evaluation, and improving surgical precision. Many of these applications have begun to mitigate risks of intraoperative and postoperative complications and post-operative care. This article aims to present an overview of the principal published papers on the significant themes of tumor, spine, epilepsy, and vascular issues, wherein AI has been applied to assess its potential applications within neurosurgery. The method involved identifying high-cited seminal papers using PubMed and Google Scholar, conducting a comprehensive review of various study types, and summarizing machine learning applications to enhance understanding among clinicians for future utilization. Recent studies demonstrate that machine learning (ML) holds significant potential in neuro-oncological care, spine surgery, epilepsy management, and other neurosurgical applications. ML techniques have proven effective in tumor identification, surgical outcomes prediction, seizure outcome prediction, aneurysm prediction, and more, highlighting its broad impact and potential in improving patient management and outcomes in neurosurgery. This review will encompass the current state of research, as well as predictions for the future of AI within neurosurgery.