Current status of artificial intelligence technologies in pituitary adenoma surgery: a scoping review.

PURPOSE: Pituitary adenoma surgery is a complex procedure due to critical adjacent neurovascular structures, variations in size and extensions of the lesions, and potential hormonal imbalances. The integration of artificial intelligence (AI) and machine learning (ML) has demonstrated considerable potential in assisting neurosurgeons in decision-making, optimizing surgical outcomes, and providing real-time feedback. This scoping review comprehensively summarizes the current status of AI/ML technologies in pituitary adenoma surgery, highlighting their strengths and limitations. METHODS: PubMed, Embase, Web of Science, and Scopus were searched following the PRISMA-ScR guidelines. Studies discussing the use of AI/ML in pituitary adenoma surgery were included. Eligible studies were grouped to analyze the different outcomes of interest of current AI/ML technologies. RESULTS: Among the 2438 identified articles, 44 studies met the inclusion criteria, with a total of seventeen different algorithms utilized across all studies. Studies were divided into two groups based on their input type: clinicopathological and imaging input. The four main outcome variables evaluated in the studies included: outcome (remission, recurrence or progression, gross-total resection, vision improvement, and hormonal recovery), complications (CSF leak, readmission, hyponatremia, and hypopituitarism), cost, and adenoma-related factors (aggressiveness, consistency, and Ki-67 labeling) prediction. Three studies focusing on workflow analysis and real-time navigation were discussed separately. CONCLUSION: AI/ML modeling holds promise for improving pituitary adenoma surgery by enhancing preoperative planning and optimizing surgical strategies. However, addressing challenges such as algorithm selection, performance evaluation, data heterogeneity, and ethics is essential to establish robust and reliable ML models that can revolutionize neurosurgical practice and benefit patients.

Awake craniotomy during pregnancy: A systematic review of the published literature.

Neurosurgical pathologies in pregnancy pose significant complications for the patient and fetus, and physiological stressors during anesthesia and surgery may lead to maternal and fetal complications. Awake craniotomy (AC) can preserve neurological functions while reducing exposure to anesthetic medications. We reviewed the literature investigating AC during pregnancy. PubMed, Scopus, and Web of Science databases were searched from the inception to February 7th, 2023, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline. Studies in English investigating AC in pregnant patients were included in the final analysis. Nine studies composed of nine pregnant patients and ten fetuses (one twin-gestating patient) were included. Glioma was the most common pathology reported in six (66.7%) patients. The frontal lobe was the most involved region (4 cases, 44.4%), followed by the frontoparietal region (2 cases, 22.2%). The awake-awake-awake approach was the most common protocol in seven (77.8%) studies. The shortest operation time was two hours, whereas the longest one was eight hours and 29 min. The mean gestational age at diagnosis was 13.6 ± 6.5 (2-22) and 19.6 ± 6.9 (9-30) weeks at craniotomy. Seven (77.8%) studies employed intraoperative fetal heart rate monitoring. None of the AC procedures was converted to general anesthesia. Ten healthy babies were delivered from patients who underwent AC. In experienced hands, AC for resection of cranial lesions of eloquent areas in pregnant patients is safe and feasible and does not alter the pregnancy outcome.

Comparative Assessment of Biomechanical Parameters in Subjects With Multiple Cerebral Aneurysms Using Fluid-Structure Interaction Simulations.

Cerebral aneurysm progression is a result of a complex interplay of the biomechanical and clinical risk factors that drive aneurysmal growth and rupture. Subjects with multiple aneurysms are unique cases wherein clinical risk factors are expected to affect each aneurysm equally, thus allowing for disentangling the effect of biomechanical factors on aneurysmal growth. Toward this end, we performed a comparative computational fluid-structure interaction analysis of aneurysmal biomechanics in image-based models of stable and growing aneurysms in the same subjects, using the cardiovascular simulation platform simvascular. We observed that areas exposed to low shear and the median peak systolic arterial wall displacement were higher by factors of 2 or more and 1.5, respectively, in growing aneurysms as compared to stable aneurysms. Furthermore, we defined a novel metric, the oscillatory stress index (OStI), which indicates locations of oscillating arterial wall stresses. We observed that growing aneurysms were characterized by regions of combined low wall shear and high OStI, which we hypothesize to be associated with regions of collagen degradation and remodeling. Such regions were either absent or below 5% of the surface area in stable aneurysms. Our results lay the groundwork for future studies in larger cohorts of subjects, to evaluate the statistical significance of these biomechanical parameters in cerebral aneurysm growth.

Functional expression of CD73 on human natural killer cells.

The production of adenosine by CD73 on cancer cells in the tumor microenvironment is a recognized immunosuppressive mechanism contributing to immune evasion in many solid tumors. While NK cells have been purported to overexpress CD73 under certain conditions, this phenomenon has remained elusive and unclear. We have found that while NK cells are able to upregulate expression of CD73 on their surface when exposed to CD73+ cancer cells, this upregulation is not universal, nor is it often substantial. Rather, our data point to the extent of CD73 expression on NK cells to be both cancer-specific and environmentally-driven, and largely limited in intensity. We found that NK cell overexpression of CD73 responds to the level of CD73 on cancer cells and is enhanced in hypoxia. Interestingly, human CD73+ NK cells appear hyperfunctional in vitro compared to CD73- NK cells, suggesting that CD73 expression could be a bystander of NK cell activation. In addition, glioblastoma patient data show that tumor-infiltrating NK cells express CD73 variably, depending on donor, and present lower expression of CD16, alongside patient-specific changes in CEACAM1, CXCR3 and TIM-3, suggesting some functional changes in NK cell responses associated with expression of CD73 on NK cells in vivo. Taken together, our study is the first to show that while NK cells are largely resistant to the upregulation of CD73, CD73 expression is inducible on NK cells in response to CD73 on cancer cells, and these cells are associated with distinct functional signatures.

Hemodynamics of Cerebral Aneurysms: Connecting Medical Imaging and Biomechanical Analysis.

In the last two decades, numerous studies have conducted patient-specific computations of blood flow dynamics in cerebral aneurysms and reported correlations between various hemodynamic metrics and aneurysmal disease progression or treatment outcomes. Nevertheless, intra-aneurysmal flow analysis has not been adopted in current clinical practice, and hemodynamic factors usually are not considered in clinical decision making. This review presents the state of the art in cerebral aneurysm imaging and image-based modeling, discussing the advantages and limitations of each approach and focusing on the translational value of hemodynamic analysis. Combining imaging and modeling data obtained from different flow modalities can improve the accuracy and fidelity of resulting velocity fields and flow-derived factors that are thought to affect aneurysmal disease progression. It is expected that predictive models utilizing hemodynamic factors in combination with patient medical history and morphological data will outperform current risk scores and treatment guidelines. Possible future directions include novel approaches enabling data assimilation and multimodality analysis of cerebral aneurysm hemodynamics.

Primary and radiation induced skull base osteosarcoma: a systematic review of clinical features and treatment outcomes.

PURPOSE: We aim to systematically review and summarize the demographics, clinical features, management strategies, and clinical outcomes of primary and radiation-induced skull-base osteosarcoma (SBO). METHODS: PubMed, Scopus, and Cochrane databases were used to identify relevant articles. Papers including SBO cases and sufficient clinical outcome data were included. A comprehensive clinical characteristic review and survival analysis were also conducted. RESULTS: Forty-one studies describing 67 patients were included. The median age was 31 years (male = 59.7%). The middle skull-base was most commonly involved (52.7%), followed by anterior (34.5%) and posterior (12.7%) skull-base. Headache (27%), exophthalmos (18%), and diplopia (10%) were common presenting symptoms. Sixty-eight percent of patients had primary SBO, while 25% had radiation-induced SBO. Surgery was the main treatment modality in 89% of cases. Chemotherapy was administered in 65.7% and radiotherapy in 50%. Median progression-free survival (PFS) was 12 months, and the overall 5-year survival was 22%. The five-year survival rates of radiation-induced SBO and primary SBO were 39% and 16%, respectively (P < 0.05). CONCLUSION: SBO is a malignant disease with poor survival outcomes. Surgical resection is the primary management modality, in conjunction with chemotherapy and radiotherapy. Radiation-induced SBO has a superior survival outcome as compared to its primary counterpart. Complete surgical resection showed a statistically insignificant survival benefit as compared to partial resection.

Higher Monocyte Count is Associated with 30-Day Case Fatality in Intracerebral Hemorrhage.

BACKGROUND: Previous studies have suggested that elevated neutrophils, monocytes, and neutrophil-to-lymphocyte ratio (NLR) may be associated with poor outcomes in intracerebral hemorrhage (ICH). We sought to determine whether white blood cell (WBC) types were independently associated with poor outcome in ICH in a large cohort. METHODS: We performed a retrospective study of primary ICH at two academic centers. Cases were identified via ICD-9 code and verified via physician review. We included only those patients with WBC types obtained within 24 h of ICH onset. RESULTS: We identified 593 patients with primary ICH and WBC differentials in the first 24 h. Independent factors (OR, 95% CI) associated with 30-day case fatality were age > 80 (2.4 (1.4, 4.2)), p = 0.0023; NIHSS greater than median (3.9 (2.4, 6.3)), p < 0.0001; ICH volume quartiles (Q1: ref, Q2: 1.5 (0.7, 3.0), Q3: 3.2 (1.6, 6.6), Q4: 11.9 (5.3, 26.4)), p < 0.0001; non-lobar location (3.3 (1.9, 5.9)), p ≤ 0.0001; IVH (2.3 (1.4, 3.6)), p = 0.0005, monocytes greater than median (1.6 (1.0, 2.4)), p = 0.0457, and anticoagulant use (3.2 (1.8, 5.6)), p < 0.0001. Elevated NLR was not associated with higher case fatality. CONCLUSIONS: We found that elevated monocytes were independently associated with 30-day case fatality. Future studies will investigate whether there are subgroups of ICH patients, including those with particular blood or imaging biomarkers, in which WBC types might help predict poor outcome and provide targets for intervention.

Intraoperative assessment of tumor margins during glioma resection by desorption electrospray ionization-mass spectrometry.

Intraoperative desorption electrospray ionization-mass spectrometry (DESI-MS) is used to characterize tissue smears by comparison with a library of DESI mass spectra of pathologically determined tissue types. Measurements are performed in the operating room within 3 min. These mass spectra provide direct information on tumor infiltration into white or gray brain matter based on N-acetylaspartate (NAA) and on membrane-derived complex lipids. The mass spectra also indicate the isocitrate dehydrogenase mutation status of the tumor via detection of 2-hydroxyglutarate, currently assessed postoperatively on biopsied tissue using immunohistochemistry. Intraoperative DESI-MS measurements made at surgeon-defined positions enable assessment of relevant disease state of tissue within the tumor mass and examination of the resection cavity walls for residual tumor. Results for 73 biopsies from 10 surgical resection cases show that DESI-MS allows detection of glioma and estimation of high tumor cell percentage (TCP) at surgical margins with 93% sensitivity and 83% specificity. TCP measurements from NAA are corroborated by indirect measurements based on lipid profiles. Notably, high percentages (>50%) of unresected tumor were found in one-half of the margin biopsy smears, even in cases where postoperative MRI suggested gross total tumor resection. Unresected tumor causes recurrence and malignant progression, as observed within a year in one case examined in this study. These results corroborate the utility of DESI-MS in assessing surgical margins for maximal safe tumor resection. Intraoperative DESI-MS analysis of tissue smears, ex vivo, can be inserted into the current surgical workflow with no alterations. The data underscore the complexity of glioma infiltration.

The Neurosurgical Atlas: advancing neurosurgical education in the digital age.

OBJECTIVE: The advent of the internet and the popularity of e-learning resources has promoted a shift in medical and surgical education today. The Neurosurgical Atlas has sought to capitalize on this shift by providing easily accessible video and online education to its users on an international scale. The rising popularity of social media has provided new avenues for expanding that global reach, and the Atlas has sought to do just that. In this study, the authors analyzed user demographics and web traffic patterns to quantify the international reach of the Atlas and examined the potential impact of social media platforms on the expansion of that reach. METHODS: Twitter, Facebook, and Instagram metrics were extracted using each respective service's analytics tool from the date of their creation through October 2019. Google Analytics was used to extract website traffic data from September 2018 to September 2019 and app data from January 2019 to October 2019. The metrics extracted included the number of platform users/followers, user demographic information, percentage of new versus returning visitors, and a number of platform-specific values. RESULTS: Since the authors' previous publication in 2017, annual website viewership has more than doubled to greater than 500,000 viewing sessions in the past year alone; international users accounted for more than 60% of the visits. The Atlas Twitter account, established in August 2012, has more than 12,000 followers, primarily hailing from the United States, the United Kingdom, Canada, and Saudi Arabia. The Atlas Facebook account, established in 2013, has just over 13,000 followers, primarily from India, Egypt, and Mexico. The Atlas Instagram account (established most recently, in December 2018) has more than 16,000 followers and the highest percentage (31%) of younger users (aged 18-24 years). The Atlas app was officially launched in May 2019, largely via promotion on the Atlas social media platforms, and has since recorded more than 60,000 viewing sessions, 80% of which were from users outside the United States. CONCLUSIONS: The Neurosurgical Atlas has attempted to leverage the many e-learning resources at its disposal to assist in spreading neurosurgical best practice on an international scale in a novel and comprehensive way. By incorporating multiple social media platforms into its repertoire, the Atlas is able to ensure awareness of and access to these resources regardless of the user's location or platform of preference. In so doing, the Atlas represents a novel way of advancing access to neurosurgical educational resources in the digital age.

Online Impact and Presence of a Specialized Social Media Team for the Journal of Neurosurgery: Descriptive Analysis.

BACKGROUND: Social media use continues to gain momentum in academic neurosurgery. To increase journal impact and broaden engagement, many scholarly publications have turned to social media to disseminate research. The Journal of Neurosurgery Publishing Group (JNSPG) established a dedicated, specialized social media team (SMT) in November 2016 to provide targeted improvement in digital outreach. OBJECTIVE: The goal of this study was to examine the impact of the JNSPG SMT as measured by increased engagement. METHODS: We analyzed various metrics, including impressions, engagements, retweets, likes, profile clicks, and URL clicks, from consecutive social media posts from the JNSPG's Twitter and Facebook platforms between February 1, 2015 and February 28, 2019. Standard descriptive statistics were utilized. RESULTS: Between February 2015 and October 2016, when a specialized SMT was created, 170 tweets (8.1 tweets/month) were posted compared to 3220 tweets (115.0 tweets/month) between November 2016 and February 2019. All metrics significantly increased, including the impressions per tweet (mean 1646.3, SD 934.9 vs mean 4605.6, SD 65,546.5; P=.01), engagements per tweet (mean 35.2, SD 40.6 vs mean 198.2, SD 1037.2; P<.001), retweets (mean 2.5, SD 2.8 vs mean 10.5, SD 15.3; P<.001), likes (mean 2.5, SD 4.0 vs mean 18.0, SD 37.9; P<.001), profile clicks (mean 1.5, SD 2.0 vs mean 5.2, SD 43.3; P<.001), and URL clicks (mean 13.1, SD 14.9 vs mean 38.3, SD 67.9; P<.001). Tweets that were posted on the weekend compared to weekdays had significantly more retweets (mean 9.2, SD 9.8 vs mean 13.4, SD 25.6; P<.001), likes (mean 15.3, SD 17.9 vs mean 23.7, SD 70.4; P=.001), and URL clicks (mean 33.4, SD 40.5 vs mean 49.5, SD 117.3; P<.001). Between November 2015 and October 2016, 49 Facebook posts (2.3 posts/month) were sent compared to 2282 posts (81.5 posts/month) sent between November 2016 and February 2019. All Facebook metrics significantly increased, including impressions (mean 5475.9, SD 5483.0 vs mean 8506.1, SD 13,113.9; P<.001), engagements (mean 119.3, SD 194.8 vs mean 283.8, SD 733.8; P<.001), and reach (mean 2266.6, SD 2388.3 vs mean 5344.1, SD 8399.2; P<.001). Weekend Facebook posts had significantly more impressions per post (mean 7967.9, SD 9901.0 vs mean 9737.8, SD 19,013.4; P=.03) and a higher total reach (mean 4975.8, SD 6309.8 vs mean 6108.2, SD 12,219.7; P=.03) than weekday posts. CONCLUSIONS: Social media has been established as a crucial tool for the propagation of neurosurgical research and education. Implementation of the JNSPG specialized SMT had a demonstrable impact on increasing the online visibility of social media content.

Cerebral circulation time derived from fMRI signals in large blood vessels.

BACKGROUND: The systemic low-frequency oscillation (sLFO) functional (f)MRI signals extracted from the internal carotid artery (ICA) and the superior sagittal sinus (SSS) are found to have valuable physiological information. PURPOSE: 1) To further develop and validate a method utilizing these signals to measure the delay times from the ICAs and the SSS. 2) To establish the delay time as an effective perfusion biomarker that associates with cerebral circulation time (CCT). 3) To explore within subject variations, and the effects of gender and age on the delay times. STUDY TYPE: Prospective. SUBJECTS: In all, 100 healthy adults (Human Connectome Project [HCP], age range 22-36 years, 54 females and 46 males), 56 healthy children (Adolescent Brain Cognitive Development project) were included. FIELD STRENGTH/SEQUENCE: Echo planar imaging (EPI) sequence at 3T. ASSESSMENT: The sLFO fMRI signals from the ICAs and the SSSs were extracted from the resting state fMRI data. The maximum cross-correlation coefficients and their corresponding delay times were calculated. The gender and age differences of delay times were assessed statistically. STATISTICAL TESTS: T-tests were conducted to measure the gender differences. The Kruskal-Wallis test was used to detect age differences. RESULTS: Consistent and robust results were found from 80% of the 400 HCP scans included. Negative correlations (-0.67) between the ICA and the SSS signals were found with the ICA signal leading the SSS signal by ∼5 sec. Within subject variation was 2.23 sec at the 5% significance level. The delay times were not significantly different between genders (P = 0.9846, P = 0.2288 for the left and right ICA, respectively). Significantly shorter delay times (4.3 sec) were found in the children than in the adults (P < 0.01). DATA CONCLUSION: We have shown that meaningful perfusion information (ie, CCT) can be derived from the sLFO fMRI signals of the large blood vessels. LEVEL OF EVIDENCE: 1 Technical Efficacy Stage: 1 J. Magn. Reson. Imaging 2019;50:1504-1513.

Intraoperative detection of isocitrate dehydrogenase mutations in human gliomas using a miniature mass spectrometer.

Knowledge of the isocitrate dehydrogenase (IDH) mutation status of glioma patients could provide insights for decision-making during brain surgery. However, pathology is not able to provide such information intraoperatively. Here we describe the first application of a miniature mass spectrometer (MS) to the determination of IDH mutation status in gliomas intraoperatively. The instrumentation was modified to be compatible with use in the operating room. Tandem MS was performed on the oncometabolite, 2-hydroxyglutarate, and a reference metabolite, glutamate, which is not involved in the IDH mutation. Ratios of fragment ion intensities were measured to calculate an IDH mutation score, which was used to differentiate IDH mutant and wild-type tissues. The results of analyzing 25 biopsies from 13 patients indicate that reliable determination of IDH mutation status was achieved (p = 0.0001, using the Kruskal-Wallis non-parametric test). With its small footprint and low power consumption and noise level, this application of miniature mass spectrometers represents a simple and cost-effective platform for an important intraoperative measurement. Graphical abstract.

Lipid and metabolite profiles of human brain tumors by desorption electrospray ionization-MS.

Examination of tissue sections using desorption electrospray ionization (DESI)-MS revealed phospholipid-derived signals that differ between gray matter, white matter, gliomas, meningiomas, and pituitary tumors, allowing their ready discrimination by multivariate statistics. A set of lower mass signals, some corresponding to oncometabolites, including 2-hydroxyglutaric acid and N-acetyl-aspartic acid, was also observed in the DESI mass spectra, and these data further assisted in discrimination between brain parenchyma and gliomas. The combined information from the lipid and metabolite MS profiles recorded by DESI-MS and explored using multivariate statistics allowed successful differentiation of gray matter (n = 223), white matter (n = 66), gliomas (n = 158), meningiomas (n = 111), and pituitary tumors (n = 154) from 58 patients. A linear discriminant model used to distinguish brain parenchyma and gliomas yielded an overall sensitivity of 97.4% and a specificity of 98.5%. Furthermore, a discriminant model was created for tumor types (i.e., glioma, meningioma, and pituitary), which were discriminated with an overall sensitivity of 99.4% and a specificity of 99.7%. Unsupervised multivariate statistics were used to explore the chemical differences between anatomical regions of brain parenchyma and secondary infiltration. Infiltration of gliomas into normal tissue can be detected by DESI-MS. One hurdle to implementation of DESI-MS intraoperatively is the need for tissue freezing and sectioning, which we address by analyzing smeared biopsy tissue. Tissue smears are shown to give the same chemical information as tissue sections, eliminating the need for sectioning before MS analysis. These results lay the foundation for implementation of intraoperative DESI-MS evaluation of tissue smears for rapid diagnosis.

Analysis of human gliomas by swab touch spray-mass spectrometry: applications to intraoperative assessment of surgical margins and presence of oncometabolites.

Touch spray mass spectrometry using medical swabs is an ambient ionization technique (ionization of unprocessed sample in the open air) that has potential intraoperative application in quickly identifying the disease state of tissue and in better characterizing the resection margin. To explore this potential, we studied 29 human brain tumor specimens and obtained evidence that this technique can provide diagnostic molecular information that is relevant to brain cancer. Touch spray using medical swabs involves the physical sampling of tissue using a medical swab on a spatial scale of a few mm2 with subsequent ionization occurring directly from the swab tip upon addition of solvent and application of a high voltage. Using a tertiary mixture of acetonitrile, N,N-dimethylformamide, and ethanol, membrane-derived phospholipids and oncometabolites are extracted from the tissue, incorporated into the sprayed microdroplets, vacuumed into the mass spectrometer, and characterized in the resulting mass spectra. The tumor cell load was assessed from the complex phospholipid pattern in the mass spectra and also separately by measurement of N-acetylaspartate. Mutation status of the isocitrate dehydrogenase gene was determined via detection of the oncometabolite 2-hydroxyglutarate. The lack of sample pretreatment makes touch spray mass spectrometry using medical swabs a feasible intraoperative strategy for rapid surgical assessment.

Prophylactic Anticonvulsants in Intracerebral Hemorrhage.

BACKGROUND AND PURPOSE: Prophylactic anticonvulsants are routinely prescribed in the acute setting for intracerebral hemorrhage (ICH) patients, but some studies have reported an association with worse outcomes. We sought to characterize the prevalence and predictors of prophylactic anticonvulsant administration after ICH as well as guideline adherence. We also sought to determine whether prophylactic anticonvulsants were independently associated with poor outcome. METHODS: We performed a retrospective study of primary ICH in our two academic centers. We used a propensity matching approach to make treated and non-treated groups comparable. We conducted multiple logistic regression analysis to identify independent predictors of prophylactic anticonvulsant initiation and its association with poor outcome as measured by modified Rankin score. RESULTS: We identified 610 patients with primary ICH, of whom 98 were started on prophylactic anticonvulsants. Levetiracetam (97%) was most commonly prescribed. Age (OR 0.97, 95% CI 0.95-0.99, p < .001), lobar location (OR 2.94, 95% CI 1.76-4.91, p < .001), higher initial National Institutes of Health Stroke Scale (NIHSS) score (OR 2.31, 95% CI 1.40-3.79, p = .001), craniotomy (OR 3.06, 95% CI 1.51-6.20, p = .002), and prior ICH (OR 2.36, 95% CI 1.10-5.07, p = .028) were independently associated with prophylactic anticonvulsant initiation. Prophylactic anticonvulsant use was not associated with worse functional outcome [modified Rankin score (mRS) 4-6] at hospital discharge or with increased case-fatality. There was no difference in prescribing patterns after 2010 guideline publication. DISCUSSION: Levetiracetam was routinely prescribed following ICH and was not associated with worse outcomes. Future investigations should examine the effect of prophylactic levetiracetam on cost and neuropsychological outcomes as well as the role of continuous EEG in identifying subclinical seizures.

The Role of MDM2 in Promoting Genome Stability versus Instability.

In cancer, the mouse double minute 2 (MDM2) is an oncoprotein that contributes to the promotion of cell growth, survival, invasion, and therapeutic resistance. The impact of MDM2 on cell survival versus cell death is complex and dependent on levels of MDM2 isoforms, p53 status, and cellular context. Extensive investigations have demonstrated that MDM2 protein-protein interactions with p53 and other p53 family members (p63 and p73) block their ability to function as transcription factors that regulate cell growth and survival. Upon genotoxic insults, a dynamic and intricately regulated DNA damage response circuitry is activated leading to release of p53 from MDM2 and activation of cell cycle arrest. What ensues following DNA damage, depends on the extent of DNA damage and if the cell has sufficient DNA repair capacity. The well-known auto-regulatory loop between p53-MDM2 provides an additional layer of control as the cell either repairs DNA damage and survives (i.e., MDM2 re-engages with p53), or undergoes cell death (i.e., MDM2 does not re-engage p53). Furthermore, the decision to live or die is also influenced by chromatin-localized MDM2 which directly interacts with the Mre11-Rad50-Nbs1 complex and inhibits DNA damage-sensing giving rise to the potential for increased genome instability and cellular transformation.

Resection of large recurrent third ventricular epidermoid tumors through the posterior interhemispheric transcallosal approach.

Epidermoid cysts or tumors comprise 1% of intracranial tumors with a predilection for the cerebellopontine angle or parasellar cisterns. These tumors are derived from an ectopic ectodermal implant seeded between fusing ectodermal surfaces. This results in a benign proliferation of stratified squamous epithelium along a cyst wall with a lumen composed of hyperkeratotic material derived from the desquamating cells. Surgical intervention is the treatment of choice for symptomatic patients. There is no role for radiotherapy or chemotherapy in the treatment of these lesions, including for residual or recurrent disease. The inherent adhesion of the proliferating epithelial lining to surrounding neurovascular structures significantly complicates attempts at gross-total resection. Epidermoid tumors or cysts are rarely reported within the third ventricular region. In this video, the authors demonstrate the technique of right-sided posterior interhemispheric transcallosal approach for maximal resection of a complex recurrent third ventricular epidermoid tumor with lateral ventricular extension. The video can be found here: https://youtu.be/wbXp7mc0vT4 .

Outcomes in transcranial microsurgery versus extended endoscopic endonasal approach for primary resection of adult craniopharyngiomas.

OBJECTIVE Craniopharyngiomas have historically been resected via transcranial microsurgery (TCM). In the last 2 decades, the extended endoscopic endonasal (transtuberculum) approach to these tumors has become more widely accepted, yet there remains controversy over which approach leads to better outcomes. The purpose of this study is to determine whether differences in outcomes were identified between TCM and extended endoscopic endonasal approaches (EEEAs) in adult patients undergoing primary resection of suprasellar craniopharyngiomas at a single institution. METHODS A retrospective review of all patients who underwent resection of their histopathologically confirmed craniopharyngiomas at the authors' institution between 2005 and 2015 was performed. Pediatric patients, revision cases, and patients with tumors greater than 2 standard deviations above the mean volume were excluded. The patients were divided into 2 groups: those undergoing primary TCM and those undergoing a primary EEEA. Preoperative patient demographics, presenting symptoms, and preoperative tumor volumes were determined. Extent of resection, tumor histological subtype, postoperative complications, and additional outcome data were obtained. Statistical significance between variables was determined utilizing Student t-tests, chi-square tests, and Fisher exact tests when applicable. RESULTS After exclusions, 21 patients satisfied the aforementioned inclusion criteria; 12 underwent TCM for resection while 9 benefitted from the EEEA. There were no significant differences in patient demographics, presenting symptoms, tumor subtype, or preoperative tumor volumes; no tumors had significant lateral or prechiasmatic extension. The extent of resection was similar between these 2 groups, as was the necessity for additional surgery or adjuvant therapy. CSF leakage was encountered only in the EEEA group (2 patients). Importantly, the rate of postoperative visual improvement was significantly higher in the EEEA group than in the TCM group (88.9% vs 25.0%; p = 0.0075). Postoperative visual deterioration only occurred in the TCM group (3 patients). Recurrence was uncommon, with similar rates between the groups. Other complication rates, overall complication risk, and additional outcome measures were similar between these groups as well. CONCLUSIONS Based on this study, most outcome variables appear to be similar between TCM and EEEA routes for similarly sized tumors in adults. The multidisciplinary EEEA to craniopharyngioma resection represents a safe and compelling alternative to TCM. The authors' data demonstrate that postoperative visual improvement is statistically more likely in the EEEA despite the increased risk of CSF leakage. These results add to the growing evidence that the EEEA may be considered the approach of choice for resection of select confined primary craniopharyngiomas without significant lateral extension in centers with experienced surgeons. Further prospective, multiinstitutional collaboration is needed to power studies capable of fully evaluating indications and appropriate approaches for craniopharyngiomas.

Neural connections between the nervus intermedius and the facial and vestibulocochlear nerves in the cerebellopontine angle: an anatomic study.

PURPOSE: Unexpected clinical outcomes following transection of single nerves of the internal acoustic meatus have been reported. Therefore, this study aimed to investigate interneural connections between the nervus intermedius and the adjacent nerves in the cerebellopontine angle. METHODS: On 100 cadaveric sides, dissections were made of the facial/vestibulocochlear complex in the cerebellopontine angle with special attention to the nervus intermedius and potential connections between this nerve and the adjacent facial or vestibulocochlear nerves. RESULTS: A nervus intermedius was identified on all but ten sides. Histologically confirmed neural connections were found between the nervus intermedius and either the facial or vestibulocochlear nerves on 34 % of sides. The mean diameter of these small interconnecting nerves was 0.1 mm. The fiber orientation of these nerves was usually oblique (anteromedial or posterolateral) in nature, but 13 connections traveled anteroposteriorly. Connecting fibers were single on 81 % of sides, doubled on 16 %, and tripled on 3 %, six sides had connections both with the facial nerve anteriorly and the vestibular nerves posteriorly. On 6.5 % of sides, a connection was between the nervus intermedius and cochlear nerve. For vestibular nerve connections with the nervus intermedius, 76 % were with the superior vestibular nerve and 24 % with the inferior vestibular nerve. CONCLUSIONS: Knowledge of the possible neural interconnections found between the nervus intermedius and surrounding nerves may prove useful to surgeons who operate in these regions so that inadvertent traction or transection is avoided. Additionally, unanticipated clinical presentations and exams following surgery may be due to such neural interconnections.

Proton therapy for atypical meningiomas.

We report clinical outcomes of proton therapy in patients with World Health Organization grade 2 (atypical) meningiomas. Between 2005 and 2013, 22 patients with atypical meningiomas were treated to a median dose of 63 Gy (RBE) using proton therapy, as an adjuvant therapy after surgery (n = 12) or for recurrence or progression of residual tumor (n = 10). Six patients had presumed radiation-induced meningiomas, but none had received prior radiotherapy for their meningioma. The median follow-up time after radiation was 39 months (range 7-104) and all patients remain alive at last follow-up. The 5-year estimate of local control was 71.1% (95% CI 49.3-92.9%). The 5-year estimate of local control was 87.5% following a radiation dose >60 Gy (RBE), compared to 50.0% for ≤ 60 Gy (RBE) (p = 0.038). The 5-year estimate of neuraxis dissemination was 5% (95% CI 0-14.6%) and 6.2% (95% CI 0-18.2%) for metastases outside of the central nervous system. Radiation necrosis was observed in one patient with a history of prior cranial irradiation. Fractionated proton therapy was associated with favorable tumor control rates for grade 2 meningiomas. Prospective studies are needed to define the optimal radiation dose for high-grade meningiomas.