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The Simpson grading scale, developed in 1957 by Donald Simpson, has been considered the gold standard for defining the surgical extent of resection for WHO grade I meningiomas. Since its introduction, the scale and its modifications have generated enormous controversy. The Simpson grade is based on an intraoperative visual assessment of resection, which is subjective and notoriously inaccurate. The majority of studies in which the grading system was used were performed before routine postoperative MRI surveillance was employed, rendering assessments of extent of resection and the definition of recurrence inconsistent. The infiltration and proliferation potential of tumor components such as hyperostotic bone and dural tail vary widely based on tumor location, as does the molecular biology of the tumor, rendering a universal scale for all meningiomas unfeasible. While extent of resection is clearly important at reducing recurrence rates, achieving the highest Simpson grade resection should not always be the goal of surgery. Donald Simpson's name and his scale deserve to be recognized and preserved in the historical pantheon of pioneering and transformative neurosurgical concepts. Nevertheless, his eponymous scale is no longer relevant in modern meningioma surgery. While his message of maximizing extent of resection and minimizing morbidity is still germane, a single measure using subjective criteria cannot be applied universally to all meningiomas, regardless of location. Meningioma surgery should be performed with the goal of achieving maximal safe resection, ideally guided by molecularly tagged fluorescent labeling and assessed using objective criteria, including postoperative MRI as well as molecularly tagged scans such as [68Ga]-DOTATATE-PET.

Background: Endonasal endoscopic transsphenoidal surgery (EETS) for pituitary adenoma has become a mainstay of treatment over the last two decades and it is generally accepted that once this learning curve is achieved, a plateau is reached with little incremental improvement., Objective: The objective of this study was to assess the slope of the learning curve over a long period of time for a variety of outcomes measures., Methods: We examined outcomes and complications in a consecutive series of 600 EETS for pituitary adenoma grouped into quartiles based on date of surgery., Results: GTR significantly increased across quartiles from 55 to 79% in the last quartile (p < 0.005). The rate of intraoperative CSF leak significantly decreased from 60% in the first quartile to 33% in the last quartile and the rate of lumbar drain placement from 28% in the first quartile to 6% in the last quartile (p < 0.005). Hormonal remission for secreting adenomas increased from 68% in the first quartile to 90% in the last quartile (p < 0.05). The rate of post-operative CSF leak trended lower (3% in first quartile to 0.7% in last two quartiles). The greatest improvement in outcome occurred between the first and second quartiles (19.9%), but persistent improvement occurred between the second and third (6.7%) and third and fourth quartiles (8.0%)., Conclusion: Although the slope of the learning curve is steeper earlier in a surgeon's experience, the slope does not plateau and continues to increase even over more than a decade.

Background: Spontaneous sphenoid sinus cerebrospinal fluid (CSF) encephaloceles have been postulated to arise from a persistent Sternberg's canal. However, recent evidence has questioned this embryological etiology. We examined the anatomic location of a series of lateral sphenoid sinus encephaloceles to determine if they corresponded with the location of Sternberg's canal., Methods: We queried a prospectively acquired database of surgically treated spontaneous CSF leaks and identified those arising from the sphenoidal sinus. Images were reviewed to characterize the leaks with respect to the foramen rotundum (FR) and the vidian canal (VC). Four leak types were classified of which Type I (medial to FR and VC entering nasopharynx) was theoretically located in the precise location of Sternberg's canal. Type II was medial to FR; Type III was lateral to FR; Type IV passed through an enlarged FR into sphenoid sinus. Demographic data were analyzed., Results: Of 103 repaired CSF leaks, 17 arose from the lateral sphenoid sinus. There were no true Type I leaks, 3 Type II leaks, 12 Type III leaks, and 2 Type IV leaks. No differences were found with respect to sphenoid pneumatization, BMI, age, sex, arachnoid pits, or postoperative leak between different types., Conclusions: No evidence was found to support the existence of a classic Sternberg canal CSF leak, supporting the hypothesis that most sphenoid spontaneous leaks likely occur secondary to chronically elevated ICP. Rare cases may be related to a weakness in the sphenoid wall in the region of Sternberg's canal.

Objective: Early surgical intervention for pediatric refractory epilepsy is increasingly advocated as surgery has become safer and data have demonstrated improved outcomes with early seizure control. There is concern that the risks associated with staged invasive electroencephalography (EEG) in very young children outweigh the potential benefits. Here, the authors present a cohort of children with refractory epilepsy who were referred for invasive monitoring, and they evaluate the role and safety of staged invasive EEG in those 3 years old and younger., Methods: The authors conducted a retrospective review of children 3 years and younger with epilepsy, who had been managed surgically at two institutions between 2001 and 2015. A cohort of pediatric patients older than 3 years of age was used for comparison. Demographics, seizure etiology, surgical management, surgical complications, and adverse events were recorded. Statistical analysis was completed using Stata version 13. A p < 0.05 was considered statistically significant. Fisher's exact test was used to compare proportions., Results: Ninety-four patients (45 patients aged ≤ 3 [47.9%]) and 208 procedures were included for analysis. Eighty-six procedures (41.3%) were performed in children younger than 3 years versus 122 in the older cohort (58.7%). Forty-two patients underwent grid placement (14 patients aged ≤ 3 [33.3%]); 3 of them developed complications associated with the implant (3/42 [7.14%]), none of whom were among the younger cohort. Across all procedures, 11 complications occurred in the younger cohort versus 5 in the older patients (11/86 [12.8%] vs 5/122 [4.1%], p = 0.032). Two adverse events occurred in the younger group versus 1 in the older group (2/86 [2.32%] vs 1/122 [0.82%], p = 0.571). Following grid placement, 13/14 younger patients underwent guided resections compared to 20/28 older patients (92.9% vs 71.4%, p = 0.23)., Conclusions: While overall complication rates were higher in the younger cohort, subdural grid placement was not associated with an increased risk of surgical complications in that population. Invasive electrocorticography informs management in very young children with refractory, localization-related epilepsy and should therefore be used when clinically indicated.

Purpose: Re-irradiation of recurrent glioblastoma (GBM) may delay further recurrence but re-irradiation increases the risk of radionecrosis (RN). Salvage therapy should focus on balancing local control (LC) and toxicity. We report the results of using intraoperative Cesium-131 (Cs-131) brachytherapy for recurrent GBM in a population of patients who also received bevacizumab., Methods and Materials: Twenty patients with recurrent GBM underwent maximally safe neurosurgical resection with Cs-131 brachytherapy between 2010 and 2015. Eighty Gy was prescribed to 0.5 cm from the surface of the resection cavity. All patients previously received adjuvant radiotherapy and temozolomide, and received bevacizumab before or after salvage brachytherapy. Seven of 20 (35%) tumors were multiply recurrent and had been previously salvaged with external beam radiotherapy. Patients received MRI scans every 2 months monitored for recurrence, progression, and RN., Results: Median tumor diameter was 4.65 cm (range, 1.2-6.3 cm). Median number of seeds pace was 41 (range, 20-74) with total seed activity 96.8U (range, 41.08-201.3U). At a median followup of 19 months, crude LC was 85% and median overall survival was 9 months (range, 5-26 months). There were two postoperative wound infections (10%), three seizures (15%), and 0% incidence of RN., Conclusions: Our study demonstrates that while LC and survival are similar to other studies of postoperative external beam radiotherapy, no RN occurred in any of these patients, including 7 multiply re-irradiated patients. Of interest, there were patients with multiple recurrences whose survival extended beyond 20 months. These findings suggest that the use of highly conformal Cs-131 brachytherapy is a promising treatment for patients with recurrent GBM with minimal risk of development of RN., (Copyright © 2020 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)

Objective: To prospectively evaluate safety and efficacy of brain-responsive neurostimulation in adults with medically intractable focal onset seizures (FOS) over 9 years., Methods: Adults treated with brain-responsive neurostimulation in 2-year feasibility or randomized controlled trials were enrolled in a long-term prospective open label trial (LTT) to assess safety, efficacy, and quality of life (QOL) over an additional 7 years. Safety was assessed as adverse events (AEs), efficacy as median percent change in seizure frequency and responder rate, and QOL with the Quality of Life in Epilepsy (QOLIE-89) inventory., Results: Of 256 patients treated in the initial trials, 230 participated in the LTT. At 9 years, the median percent reduction in seizure frequency was 75% ( p < 0.0001, Wilcoxon signed rank), responder rate was 73%, and 35% had a ≥90% reduction in seizure frequency. We found that 18.4% (47 of 256) experienced ≥1 year of seizure freedom, with 62% (29 of 47) seizure-free at the last follow-up and an average seizure-free period of 3.2 years (range 1.04-9.6 years). Overall QOL and epilepsy-targeted and cognitive domains of QOLIE-89 remained significantly improved ( p < 0.05). There were no serious AEs related to stimulation, and the sudden unexplained death in epilepsy (SUDEP) rate was significantly lower than predefined comparators ( p < 0.05, 1-tailed χ 2 )., Conclusions: Adjunctive brain-responsive neurostimulation provides significant and sustained reductions in the frequency of FOS with improved QOL. Stimulation was well tolerated; implantation-related AEs were typical of other neurostimulation devices; and SUDEP rates were low., Clinicaltrialsgov Identifier: NCT00572195., Classification of Evidence: This study provides Class IV evidence that brain-responsive neurostimulation significantly reduces focal seizures with acceptable safety over 9 years., (Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

Purpose: To compare treatment plans and evaluate dosimetric characteristics of permanent cesium-131 ( 131 Cs) vs. iodine-125 ( 125 I) implants used in brain brachytherapy., Material and Methods: Twenty-four patients with 131 Cs implants from a prospective phase I/II trial were re-planned with 125 I implants. In order to evaluate the volume of brain tissue exposed to radiation therapy (RT), the dose volume histogram was generated for both radioisotopes. To evaluate the dosimetric differences of the two radioisotopes we compared homogeneity (HI) and conformity indices (CI), and dose covering 100% (D 100 ), 90% (D 90 ), 80% (D 80 ), and 50% (D 50 ) of the clinical target volume (CTV)., Results: At the 100%, 90%, 80%, and 50% isodose lines, the 131 Cs plans exposed less mean volume of brain tissue than the 125 I plans ( p < 0.001). The D 100 , D 90 , D 80 , and D 50 were smaller for 131 Cs ( p < 0.001). The HI and CI for 131 Cs vs. 125 I were 19.71 vs. 29.04 and 1.31 vs. 1.92, respectively ( p < 0.001)., Conclusions: Compared to 125 I, 131 Cs exposed smaller volumes of brain tissue to equivalent doses of radiation and delivered lower radiation doses to equivalent volumes of the CTV. 131 Cs exhibited a higher HI, indicating increased uniformity of doses within the CTV. Lastly, 131 Cs presented a CI closer to 1, indicating that the total volume receiving the prescription dose was closer to the desired CTV volume. These results suggest that 131 Cs is dosimetrically superior to 125 I and may explain the reason for the 0% incidence of radiation necrosis (RN) in our previously published prospective study using 131 Cs., Competing Interests: The authors report no conflict of interest., (Copyright © 2020 Termedia.)

Objective: The endoscopic endonasal approach (EEA) has gained increasing popularity for the resection of suprasellar meningiomas (SSMs). Appropriate case selection is critical in optimizing patient outcome. Long-term outcome data are lacking. The authors systematically identified preoperative factors associated with extent of resection (EOR) and determined the relationship between EOR and long-term recurrence after EEA for SSMs., Methods: In this retrospective cohort study, the authors identified preoperative clinical and imaging characteristics associated with EOR and built on the recently published University of California, San Francisco resectability score to propose a score more specific to the EEA. They then examined the relationship between gross-total resection (GTR; 100%), near-total resection (NTR; 95%-99%), and subtotal resection (STR; < 95%) and recurrence or progression with Kaplan-Meier survival analysis., Results: A total of 51 patients were identified. Radiographic GTR was achieved in 40 of 47 (85%) patients in whom it was the surgical goal. Significant independent risk factors for incomplete resection were prior surgery (OR 25.94, 95% CI < 2.00 to 336.49, p = 0.013); tumor lateral to the optic nerve (OR 13.41, 95% CI 1.82-98.99, p = 0.011); and complete internal carotid artery (ICA) encasement (OR 15.12, 95% CI 1.17-194.08, p = 0.037). Tumor size and optic canal invasion were not significant risk factors after adjustment for other variables. A resectability score based on the multivariable model successfully predicted the likelihood of GTR; a score of 0 had a positive predictive value of 97% for GTR, whereas a score of 2 had a negative predictive value of 87.5% for incomplete resection. After a mean follow-up of 40.6 ± 32.4 months (mean ± SD), recurrence was 2.7% after GTR (1 patient with atypical histology), 44.4% after NTR, and 80% after STR (p < 0.0001). Vision was stable or improved in 93.5% and improved in 67.4% of patients with a preoperative deficit. There were 5 (9.8%) postoperative CSF leaks, of which 4 were managed with lumbar drains and 1 required a reoperation., Conclusions: The EEA is a safe and effective approach to SSMs, with favorable visual outcomes in well-selected cases. The combination of postoperative MRI-based EOR with direct endoscopic inspection can be used in lieu of Simpson grade to predict recurrence. GTR dramatically reduces recurrence and can be achieved regardless of tumor size, proximity or encasement of the anterior cerebral artery, or medial optic canal invasion. Risk factors for incomplete resection include prior surgery, tumor lateral to the optic nerve, and complete ICA encasement.

Technical limitations and clinical challenges have historically limited the diagnostic tools and treatment methods available for surgical approaches to the management of epilepsy. By contrast, recent technological innovations in several areas hold significant promise in improving outcomes and decreasing morbidity. We review innovations in the neurosurgical management of epilepsy in several areas, including wireless recording and stimulation systems (particularly responsive neurostimulation [NeuroPace]), conformal electrodes for high-resolution electrocorticography, robot-assisted stereotactic surgery, optogenetics and optical imaging methods, novel positron emission tomography ligands, and new applications of focused ultrasonography. Investigation into genetic causes of and susceptibilities to epilepsy has introduced a new era of precision medicine, enabling the understanding of cell signaling mechanisms underlying epileptic activity as well as patient-specific molecularly targeted treatment options. We discuss the emerging path to individualized treatment plans, predicted outcomes, and improved selection of effective interventions, on the basis of these developments., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Though frequently effective in the management of medically refractory seizures, epilepsy surgery presents numerous challenges. Selection of the appropriate candidate patients who are likely to benefit from surgery is critical to achieving seizure freedom and avoiding neurocognitive morbidity. Identifying the seizure focus and mapping epileptogenic networks involves an interdisciplinary team dedicated to formulating a safe and effective surgical plan. Various strategies can be employed either to eliminate the epileptic focus or to modulate network activity, including resection of the focus with open surgery or laser interstitial thermal therapy; modulation of epileptogenic firing patterns with responsive neurostimulation, deep brain stimulation, or vagus nerve stimulation; or non-invasive disconnection of epileptic circuits with focused ultrasound, which is also discussed in greater detail in the subsequent chapter in our series. We review several challenges of epilepsy surgery that must be thoughtfully addressed in order to ensure its success., (Copyright © 2020 Elsevier Inc. All rights reserved.)

The diagnostic and surgical management of epilepsy has made enormous strides over the past 3 decades, concomitant with advances in technology and electrophysiologic understanding of neuronal connectivity. Distinct zones have been identified within this network that each communicate and play a role in the genesis of seizures. Invasive and noninvasive modalities for defining the epileptogenic lesion or region have been able to more accurately determine which patients are optimal candidates for treatment when their seizures are refractory to conventional conservative management. Ablative, palliative, and disconnecting procedures have been developed as alternatives for traditional open resection techniques, and in recent studies, they have shown excellent seizure control and mitigation of complications. In this review, we discuss the evolution of these advancements in the management of epilepsy and provide an overview of current and future neurosurgical therapeutic modalities., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background and Importance: Brainstem lesions are challenging to manage, and surgical options have been controversial. Stereotactic radiosurgery (SRS) has been used for local control, but life-threatening toxicities from 0% to 9.5% have been reported. Several microsurgical approaches involving safe entry zones have been developed to optimize the exposure and minimize complications in different portions of the brainstem, but require extensive drilling and manipulation of neurovascular structures. With recent advancements, the endoscopic endonasal approach (EEA) can provide direct visualization of ventral brainstem. No case has been reported of EEA to remove a brainstem metastasis., Clinical Presentation: We present an illustrative case of a 68-yr-old female with metastatic colon cancer who presented with 2.8 × 2.7 × 2.1 cm (7.9 cm3) heterogeneously enhancing, right ventral pontine lesion with extensive edema. She underwent endoscopic endonasal transclival approach, and gross total resection of the lesion was achieved., Conclusion: The endoscopic approach may offer certain advantages for removal of ventral brainstem lesions, as it can provide direct visualization of important neurovascular structures, especially, if the lesion displaces the tracts and comes superficial to the pial surface., (Copyright © 2019 by the Congress of Neurological Surgeons.)

Glioblastoma (GBM), an incurable tumor, remains difficult to model and more importantly to treat due to its genetic/epigenetic heterogeneity and plasticity across cellular states. The ability of current tumor models to recapitulate the cellular states found in primary tumors remains unexplored. To address this issue, we compared single-cell RNA sequencing of tumor cells from 5 patients across four patient-specific glioblastoma stem cell (GSC)-derived model types, including glioma spheres, tumor organoids, glioblastoma cerebral organoids (GLICO), and patient-derived xenografts. We find that GSCs within the GLICO model are enriched for a neural progenitor-like cell subpopulation and recapitulate the cellular states and their plasticity found in the corresponding primary parental tumors. These data demonstrate how the contribution of a neuroanatomically accurate human microenvironment is critical and sufficient for recapitulating the cellular states found in human primary GBMs, a principle that may likely apply to other tumor models. SIGNIFICANCE: It has been unclear how well different patient-derived GBM models are able to recreate the full heterogeneity of primary tumors. Here, we provide a complete transcriptomic characterization of the major model types. We show that the microenvironment is crucial for recapitulating GSC cellular states, highlighting the importance of tumor-host cell interactions. See related commentary by Luo and Weiss, p. 907 . This article is highlighted in the In This Issue feature, p. 890 ., (©2020 American Association for Cancer Research.)

Objective: Adjuvant radiation therapy (RT), such as cesium-131 (Cs-131) brachytherapy or stereotactic radiosurgery (SRS), reduces local recurrence (LR) of brain metastases (BM). However, SRS is less efficacious for large cavities, and the delay between surgery and SRS may permit tumor repopulation. Cs-131 has demonstrated improved local control, with reduced radiation necrosis (RN) compared to SRS. This study represents the first comparison of outcomes between Cs-131 brachytherapy and SRS for resected BM., Methods: Patients with BM treated with Cs-131 and SRS following gross-total resection were retrospectively identified. Thirty patients who underwent Cs-131 brachytherapy were compared to 60 controls who received SRS. Controls were selected from a larger cohort to match the patients treated with Cs-131 in a 2:1 ratio according to tumor size, histology, performance status, and recursive partitioning analysis class. Overall survival (OS), LR, regional recurrence, distant recurrence (DR), and RN were compared., Results: With a median follow-up of 17.5 months for Cs-131-treated and 13.0 months for SRS-treated patients, the LR rate was significantly lower with brachytherapy; 10% for the Cs-131 cohort compared to 28.3% for SRS patients (OR 0.281, 95% CI 0.082-0.949; p = 0.049). Rates of regional recurrence, DR, and OS did not differ significantly between the two cohorts. Kaplan-Meier analysis with log-rank testing showed a significantly higher likelihood of freedom from LR (p = 0.027) as well as DR (p = 0.018) after Cs-131 compared to SRS treatment (p = 0.027), but no difference in likelihood of OS (p = 0.093). Six (10.0%) patients who underwent SRS experienced RN compared to 1 (3.3%) patient who received Cs-131 (p = 0.417)., Conclusions: Postresection patients with BM treated with Cs-131 brachytherapy were more likely to achieve local control compared to SRS-treated patients. This study provides preliminary evidence of the potential of Cs-131 to reduce LR following gross-total resection of single BM, with minimal toxicity, and suggests the need for a prospective study to address this question.

Background: Skull base reconstruction after extended endoscopic endonasal approaches (EEAs) can be challenging. In addition to the nasoseptal flap, which has been adopted by most centers, autologous fascia lata is also often utilized. Harvesting of fascia lata requires a separate thigh incision, may prolong recovery, and results in a visible scar. In principal, the use of non-autologous materials would be preferable to avoid a second incision and maintain the minimally invasive nature of the approach, assuming the CSF leak rate is not compromised., Objective: To assess the efficacy of acellular dermal matrix (ADM) as a non-autologous alternative to autologous fascia lata graft for watertight closure of the cranial base following EEAs., Methods: A retrospective chart review of extended EEAs performed before and after the transition from fascia lata to ADM was performed. Cases were frequency matched for approach, pathology, BMI, use of lumbar drainage, and tumor volume. Power analysis was performed to estimate the sample size needed to demonstrate non-inferiority., Results: ADM was used for watertight closure of the cranial base in 19 consecutive extended endoscopic endonasal approaches (16 gasket-seals and 3 buttons) with 1 postoperative CSF leak at the last follow-up (median 5.3, range 1.0-12.6 months). All patients had high-flow intraoperative leaks. The cohort included 8 meningiomas, 8 craniopharyngiomas, 2 chordomas, and 1 pituicytoma ranging in size from 0.2 to 37.2cm 3 (median 5.5, IQR 2.8-13.3 cm 3 ). In 19 historical controls who received fascia lata, there were 2 postoperative CSF leaks., Conclusions: Preliminary results suggest that ADM provides a non-inferior non-autologous alternative to fascia lata for watertight gasket-seal and button closures following extended EEAs, potentially reducing or eliminating the need to harvest autologous tissue.

An 8-year-old child presented with fatigue, weight loss, and visual deterioration. MRI demonstrated a craniopharyngioma with compression of the optic chiasm and extensive edema on the hypothalamus and optic radiations. The tumor was completely removed via an endoscopic endonasal approach. Postoperatively, vision improved and hypothalamic edema completely resolved within 5 days. This video demonstrates the technical nuances of the surgery and discusses the impact of surgery on the hypothalamic nuclei in pediatric patients. The video can be found here: https://youtu.be/wxkBmhTPi6c., Competing Interests: Disclosures The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this publication., (© 2020, The Authors.)

Objective: Despite the rise of studies in the neurosurgical literature suggesting that patients with Medicaid insurance have inferior outcomes, there remains a paucity of data on the impact of insurance on outcomes after endonasal endoscopic transsphenoidal surgery (EETS). Given the increasing importance of complications in quality-based healthcare metrics, the objective of this study was to assess whether Medicaid insurance type influences outcomes in EETS for pituitary adenoma., Methods: The authors analyzed a prospectively acquired database of EETS for pituitary adenoma from 2005 to 2018 at NewYork-Presbyterian Hospital, Weill Cornell Medicine. All patients with Medicaid insurance were identified. As a control group, the clinical, socioeconomic, and radiographic data of all other patients in the series with non-Medicaid insurance were reviewed. Statistical significance was determined with an alpha < 0.05 using Pearson chi-square and Fisher's exact tests for categorical variables and the independent-samples t-test for continuous variables., Results: Of 584 patients undergoing EETS for pituitary adenoma, 57 (10%) had Medicaid insurance. The maximum tumor diameter was significantly larger for Medicaid patients (26.1 ± 12 vs 23.1 ± 11 mm for controls, p < 0.05). Baseline comorbidities including diabetes mellitus, hypertension, smoking history, and BMI were not significantly different between Medicaid patients and controls. Patients with Medicaid insurance had a significantly higher rate of any complication (14% vs 7% for controls, p < 0.05) and long-term cranial neuropathy (5% vs 1% for controls, p < 0.05). There were no statistically significant differences in endocrine outcome or vision outcome. The mean postoperative length of stay was significantly longer for Medicaid patients compared to the controls (9.4 ± 31 vs 3.6 ± 3 days, p < 0.05). This difference remained significant even when accounting for outliers (5.6 ± 2.5 vs 3.0 ± 2.7 days for controls, p < 0.05). The most common causes of extended length of stay greater than 1 standard deviation for Medicaid patients were management of perioperative complications and disposition challenges. The rate of 30-day readmission was 7% for Medicaid patients and 4.4% for controls, which was not a statistically significant difference., Conclusions: The authors found that larger tumor diameter, longer postoperative length of stay, higher rate of complications, and long-term cranial neuropathy were significantly associated with Medicaid insurance. There were no statistically significant differences in baseline comorbidities, apoplexy, endocrine outcome, vision outcome, or 30-day readmission.

Objective: To review indications and techniques for the endoscopic endonasal approach to the craniovertebral junction (CVJ), analyze postoperative outcomes, and discuss important technical considerations., Methods: A retrospective analysis was performed on all patients undergoing endonasal endoscopic approaches to the CVJ from May 2007 to June 2017. Demographic information, presenting symptoms, imaging results, treatment course, postoperative functional status, and follow-up were recorded., Results: There was a total of 30 patients in this series, with a mean follow-up of 11.7 months. The average age was 33.6 years (range, 5-75 years), with 18 females and 12 males. The majority of patients ( n  = 22, 73.3%) had Chiari malformation type 1 with basilar invagination and symptomatic cervicomedullary compression as the indication for surgery. Intraoperative cerebrospinal fluid leak (CSF) was noted in 3 cases of odontoid resection and a single case of skull base resection. There were no postoperative CSF leaks. Overall, 81% of patients resumed regular diet by post-operative day 2 (range, 0-8 days). Severe postoperative dysphagia occurred in two cases with one requiring gastrostomy tube placement and another utilizing total parenteral nutrition for support prior to eventual gastrostomy. On average, patients were extubated by postoperative day 0.93 (range 0-3 days), with 85% extubated by postoperative day 1. A tracheotomy was required in one patient., Conclusion: The endonasal endoscopic approach is a valuable technique for access to the CVJ with minimal disruption of respiratory and alimentary function., Competing Interests: None., (© 2020 The Authors.)

Objective: High-grade gliomas (HGGs) continue to carry poor prognoses, and patient outcomes depend heavily on the extent of resection (EOR). The utility of conventional image-guided surgery is limited by intraoperative brain shift. More recent techniques to maximize EOR, including intraoperative imaging and the use of fluorescent dyes, combat these limitations. However, the relative efficacy of these two techniques has never been systematically compared. Thus, the authors performed an exhaustive systematic review in conjunction with quantitative network meta-analyses to evaluate the comparative effectiveness of 5-aminolevulinic acid (5-ALA) and intraoperative MRI (IMRI) in optimizing EOR in HGG. They secondarily analyzed associated progression-free and overall survival and performed subgroup analyses by level of evidence., Methods: PubMed, Embase, Cochrane Central, and Web of Science were searched for studies evaluating conventional neuronavigation, IMRI, and 5-ALA in HGG resection. The primary study endpoint was the proportion of patients attaining gross-total resection (GTR), defined as 100% elimination of contrast-enhancing lesion on postoperative MRI. Secondary endpoints included overall and progression-free survival and subgroup analyses for level of evidence. Comparative efficacy analysis of IMRI and 5-ALA was performed using Bayesian network meta-analysis models., Results: This analysis included 11 studies. In a classic meta-analysis, both IMRI (OR 4.99, 95% CI 2.65-9.39, p < 0.001) and 5-ALA (OR 2.866, 95% CI 2.127-3.863, p < 0.001) were superior to conventional navigation in achieving GTR. Bayesian network analysis was employed to indirectly compare IMRI to 5-ALA, and no significant difference in GTR was found between the two (OR 1.9 favoring IMRI, 95% CI 0.905-3.989, p = 0.090). A handful of studies additionally suggested that the use of either IMRI (2 and 4 studies, respectively) or 5-ALA (2 and 2 studies, respectively) improves progression-free and overall survival., Conclusions: IMRI and 5-ALA are individually superior to conventional neuronavigation for achieving GTR of HGG. Between IMRI and 5-ALA, neither method is clearly more effective. Future studies evaluating the comparative cost and surgical time associated with IMRI and 5-ALA will better inform any cost-benefit analysis.

Objective: Endoscopic endonasal approaches (EEAs) to the skull base have evolved over the last 20 years to become an essential component of a comprehensive skull base practice. Many case series show a learning curve from the earliest cases, in which the authors were inexperienced or were not using advanced closure techniques. It is generally accepted that once this learning curve is achieved, a plateau is reached with little incremental improvement. Cases performed during the early steep learning curve were eliminated to examine whether the continued improvement exists over the "tail end" of the curve., Methods: A prospectively acquired database of all EEA cases performed by the senior authors at Weill Cornell Medicine/NewYork-Presbyterian Hospital was reviewed. The first 200 cases were eliminated and the next 1000 consecutive cases were examined to avoid the bias created by the early learning curve., Results: Of the 1000 cases, the most common pathologies included pituitary adenoma (51%), meningoencephalocele or CSF leak repair (8.6%), meningioma (8.4%), craniopharyngioma (7.3%), basilar invagination (3.1%), Rathke's cleft cyst (2.8%), and chordoma (2.4%). Use of lumbar drains decreased from the first half to the second half of our series (p <0.05) as did the authors' use of fat alone (p <0.005) or gasket alone (p <0.005) for dural closure, while the use of a nasoseptal flap increased (p <0.005). Although mean tumor diameter was constant (on average), gross-total resection (GTR) increased from 60% in the first half to 73% in the second half (p <0.005). GTR increased for all pathologies but most significantly for chordoma (56% vs 100%, p <0.05), craniopharyngioma (47% vs 0.71%, p <0.05) and pituitary adenoma (67% vs 75%, p <0.05). Hormonal cure for secreting adenomas also increased from 83% in the first half to 89% in the second half (p <0.05). The rate of any complication was unchanged at 6.4% in the first half and 6.2% in the latter half of cases, and vascular injury occurred in only 0.6% of cases. Postoperative CSF leak occurred in 2% of cases and was unchanged between the first and second half of the series., Conclusions: This study demonstrates that contrary to popular belief, the surgical learning curve does not plateau but can continue for several years depending on the complexity of the endpoints considered. These findings may have implications for clinical trial design, surgical education, and patient safety measures.

In this case report, we present a rare and previously unreported case of spontaneous regression of a histologically consistent clival chordoma. At the time of diagnosis, imaging demonstrated a T2 hyperintense and T1 isointense midline skull base mass, centered in the nasopharynx, with scalloping of the ventral clivus consistent with a chordoma measuring 3.1 × 1.9 × 3.0 cm (8.84 cm 3 ). On pre-operative imaging 2 months later, with no intervening therapy, the mass had regressed by 61.7% to a size of 2.3 × 2.1 × 1.4 cm (3.38 cm 3 ). The patient self-administered several herbal supplements and animal oils which may have contributed to tumor regression. The purpose of this report is to document this rare occurrence and provide a comprehensive description of the case details and list of the various medications, herbs, and supplements used prior to this rare event.

Objective: Nonfunctioning pituitary adenomas are benign, slow-growing tumors. After gross-total resection (GTR) or subtotal resection (STR), tumors can recur or progress and may ultimately require additional intervention. A greater understanding of long-term recurrence and progression rates following complete or partial resection and the need for further intervention will help clinicians provide meaningful counsel for their patients and assist data-driven decision-making., Methods: The authors retrospectively analyzed their institutional database for patients undergoing endoscopic endonasal surgery (EES) for nonfunctioning pituitary macroadenomas (2003-2014). Only patients with follow-up of at least 5 years after surgery were included. Tumor volumes were measured on pre- and postoperative MRI. Tumor recurrence was defined as the presence of a 0.1-cm3 tumor volume after GTR, and tumor progression was defined as a 25.0% increase in residual tumor after STR., Results: A total of 190 patients were included, with a mean age of 63.8 ± 13.2 years; 79 (41.6%) were female. The mean follow-up was 75.0 ± 18.0 months. GTR was achieved in 127 (66.8%) patients. In multivariate analysis, age (p = 0.04), preoperative tumor volume (p = 0.03), Knosp score (p < 0.001), and Ki-67 (p = 0.03) were significant predictors of STR. In patients with GTR, the probability of recurrence at 5 and 10 years was 3.9% and 4.7%, and the probability of requiring treatment for recurrence was 0.79% and 1.6%, respectively. In 63 patients who underwent STR, 6 (9.5%) received early postoperative radiation and did not experience progression, while the remaining 57 (90.5%) were observed. Of these, the probability of disease progression at 5 and 10 years was 21% and 24.5%, respectively, and the probability of requiring additional treatment for progression was 17.5% and 21%. Predictors of recurrence or progression in the entire group were Knosp score (p < 0.001) and elevated Ki-67 (p = 0.03). Significant predictors of progression after STR in those who did not receive early radiotherapy were cavernous sinus location (p < 0.05) and tumor size > 1.0 cm3 (p = 0.005)., Conclusions: Following GTR for nonfunctioning pituitary adenomas, the 10-year chance of recurrence is low and the need for treatment even lower. After STR, although upfront radiation therapy may prevent progression, even without radiotherapy, the need for intervention at 10 years is only approximately 20% and a period of observation may be warranted to prevent unnecessary prophylactic radiation therapy. Tumor volume > 1 cm3, Knosp score ≥ 3, and Ki-67 ≥ 3% may be useful metrics to prompt closer follow-up or justify early prophylactic radiation therapy.

In this chapter, we describe advances in endoscopic endonasal surgery that have impacted skull base meningioma surgery. After reviewing the technical innovations in endoscopy, we describe the advances as they relate to each surgical step. We discuss preoperative planning and approach and the utility of neuronavigation and neuromonitoring. We then discuss endoscopic instrumentation, technology for tumor debulking (ultrasonic aspirators, radiofrequency ablators, suction debriders), and hemostatic agents as they relate to tumor resection and hemostasis. In the end, we discuss techniques of skull base reconstruction and closure (nasoseptal flap, gasket seal and bilayer button)., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Interstitial intracranial radiotherapy implants, or brachytherapy, is an adjuvant option for treatment of recurrent high-grade meningiomas after resection. The implants are placed in the resection cavity following tumor resection. The most commonly used isotope is Iodine-125 (I-125). While there are no controlled studies comparing treatment of meningiomas with or without brachytherapy, several case series report good long-term survival, suggesting that this may be a useful adjuvant for recurrent high-grade tumors. Complications can occur including radiation necrosis, impaired wound healing, hydrocephalus and infection. In the future, new isotopes are being explored that may have fewer complications and better safety profiles., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Objective: The infratemporal fossa (ITF) and parapharyngeal space are anatomical regions that can be challenging to access without the use of complex, cosmetically disfiguring approaches. With advances in endoscopic techniques, a new group of surgical approaches to access the intracranial space through the orbit has been recently referred to as transorbital neuroendoscopic surgery (TONES). The objective of this study was to establish a transorbital endoscopic approach utilizing the inferior orbital fissure (IOF) to gain access to the ITF and parapharyngeal space and provide a detailed endoscopic anatomical description of this approach., Methods: Four cadaveric heads (8 sides) were dissected using a TONES approach through the IOF to reach the ITF and parapharyngeal space, providing stepwise dissection with detailed anatomical findings and a description of each step., Results: An inferior eyelid approach was made with subperiosteal periorbital dissection to the IOF. The zygomatic and greater wing of the sphenoid were drilled, forming the boundaries of the IOF. The upper head of the lateral pterygoid muscle in the ITF and parapharyngeal space was removed, and 7 distinct planes were described, each with its own anatomical contents. The second part of the maxillary artery was mainly found in plane 1 between the temporalis laterally and the lateral pterygoid muscle in plane 2. The branches of the mandibular nerve (V3) and middle meningeal artery (MMA) were identified in plane 3. Plane 4 was formed by the fascia of the medial pterygoid muscle (MTM) and the tensor veli palatini muscle. The prestyloid segment, found in plane 5, was composed mainly of fat and lymph nodes. The parapharyngeal carotid artery in the poststyloid segment, found in plane 7, was identified after laterally dissecting the styloid diaphragm, found in plane 6. V3 and the origin of the levator and tensor veli palatini muscles serve as landmarks for identification of the parapharyngeal carotid artery., Conclusions: The transorbital endoscopic approach provides excellent access to the ITF and parapharyngeal space compared to previously described complex and morbid transfacial or transcranial approaches. Using the IOF is an important and useful landmark that permits a wide exposure.

Burst suppression is an electroencephalogram pattern of globally symmetric alternating high amplitude activity and isoelectricity that can be induced by general anaesthetics. There is scattered evidence that burst suppression may become spatially non-uniform in the setting of underlying pathology. Here, we induced burst suppression with isoflurane in rodents and then created a neocortical acute seizure focus with injection of 4-aminopyridine (4-AP) in somatosensory cortex. Burst suppression events were recorded before and after creation of the focus using bihemispheric wide-field calcium imaging and multielectrode arrays. We find that the seizure focus elicits a rapid alteration in triggering, initiation, and propagation of burst suppression events. Compared with the non-seizing brain, bursts are triggered from the thalamus, initiate in regions uniquely outside the epileptic focus, elicit marked increases of multiunit activity and propagate towards the seizure focus. These findings support the rapid, widespread impact of focal epilepsy on the extended brain network., (© The Author(s) (2019). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Objective: Hospital readmission is a key component in value-based healthcare models but there are limited data about the 30-day readmission rate after endonasal endoscopic transsphenoidal surgery (EETS) for pituitary adenoma. The objective of this study was to determine the incidence and identify factors associated with 30-day readmission after EETS for pituitary adenoma., Methods: The authors analyzed a prospectively acquired database of patients who underwent EETS for pituitary adenoma from 2005 to 2018 at NewYork-Presbyterian Hospital, Weill Cornell Medicine. Clinical, socioeconomic, and radiographic data were reviewed for cases of unplanned readmission within 30 days of surgery and, as a control group, for all other patients in the series who were not readmitted. Statistical significance was determined with an alpha < 0.05 using Pearson's chi-square and Fisher's exact tests for categorical variables and the independent-samples t-test for continuous variables., Results: Of 584 patients undergoing EETS for pituitary adenoma, 27 (4.6%) had unplanned readmission within 30 days. Most readmissions occurred within the first week after surgery, with a mean time to readmission of 6.6 ± 3.9 days. The majority of readmissions (59%) were for hyponatremia. These patients had a mean sodium level of 120.6 ± 4.6 mEq/L at presentation. Other causes of readmission were epistaxis (11%), spinal headache (11%), sellar hematoma (7.4%), CSF leak (3.7%), nonspecific headache (3.7%), and pulmonary embolism (3.7%). The postoperative length of stay was significantly shorter for patients who were readmitted than for the controls (2.7 ± 1.0 days vs 3.9 ± 3.2 days; p < 0.05). Patients readmitted for hyponatremia had an initial length of stay of 2.6 ± 0.9 days, the shortest of any cause for readmission. The mean BMI was significantly lower for readmitted patients than for the controls (26.4 ± 3.9 kg/m2 vs 29.3 ± 6.1 kg/m2; p < 0.05)., Conclusions: Readmission after EETS for pituitary adenoma is a relatively rare phenomenon, with delayed hyponatremia being the primary cause. The study results demonstrate that shorter postoperative length of stay and lower BMI were associated with 30-day readmission.

After maximally safe neurosurgical resection of brain metastases, stereotactic radiosurgery (SRS) is now recommended as an alternative to whole-brain radiation therapy (WBRT), which has been associated with cognitive decline. One complicating factor associated with SRS is that postoperative cavity dynamics can change dramatically, creating significant variability in the recommended timing of SRS. While SRS has been shown to improve local control (LC) in smaller tumor cavities, achieving excellent LC rates still remains a challenge in larger ones. Furthermore, factors predicting the optimal timing of SRS in relation to the cavity size need to be defined and implemented. Variables such as the delay between postoperative MRI and treatment are critical but poorly understood. One potential treatment option that may improve outcomes is brachytherapy, but the widespread implementation of this technique has been slow. This critical review analyzes the relationship between preoperative tumor volume, resection cavity size, and timing of SRS and explores how these variables must be understood in order to achieve the highest LC possible., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2019, Yuan et al.)

Background: We report the first case of oculomotor nerve (ON) schwannoma treatment through an endonasal endoscopic approach. We also review the literature to determine prognosis factors of ON function after treatment., Methods: A complete MEDLINE search was undertaken for all articles reporting data for oculomotor schwannoma. We divided the patient population into 2 groups; Group I: patients who conserved or recovered good ON function and Group II: patients with either new, worsening, or unchanged third-nerve palsy at the last available follow-up. We conducted a comparative statistical analysis of data between the 2 groups., Results: We identified 55 reported cases of ON schwannoma, all of whom were treated with open transcranial surgery, stereotactic radiosurgery, or observation. There were 22 patients in group I and 33 in group II. At admission, 29 patients had complete oculomotor nerve palsy (34.7% in group I and 67.7% in group II; P = 0.02). Surgical treatment was performed in 36 cases. Radiosurgery was performed in 3 cases. Among patients with good preoperative ON function, 34.6% worsened at last follow-up (26.6% after surgery and 50% with observation; P = 0.03). In total, 31% of patients with total or near-total palsy at admission had an improvement of their ON function (all after surgical resection; P = 0.05)., Conclusions: ON function at admission and surgical resection of schwannoma appears to be a predictive factor of favorable prognosis regardless of location and tumor size. The endonasal endoscopic approach can be used to biopsy tumors in cases in which open surgery is considered too risky, such as cavernous sinus schwannomas., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Malignant transformation of intracranial epidermoid cysts is a rare occurrence. We present the second case of such an event occurring in the pineal region and the first case sent for detailed genomic profiling. MRI demonstrated two lesions: a cyst in a quadrigeminal cistern with restricted diffusion on DWI-weighted images and an adjacent, peripherally enhancing tumor with cerebellar infiltration. Both the lesions were completely resected with a small residual of the epidermoid cyst. The final pathology of both lesions was consistent with epidermoid cyst and squamous cell carcinoma (SCC), respectively. The tumor specimen was sent for comprehensive genomic profiling which revealed stable microsatellite status and loss of CDKN2A/B, MTAP (exons 2-8), and PTEN (exons 6-9). Although reports of primary SCC originating from the epidermoid cyst have been previously described, this is the first description of the genomic profile of such a tumor.

Background and Purpose: Meningiomas are the most common primary intracranial tumors, typically treated with surgery and adjuvant radiation in cases of subtotal resection and/or higher histopathologic grade. Contrast-enhanced magnetic resonance imaging (MRI) is the gold standard for postoperative assessment and adjuvant treatment planning. However, MRI can have limited accuracy particularly in the presence of posttreatment change. [68Ga]-DOTATATE is a Positron Emission Tomography (PET) radiotracer targeting somatostatin receptor 2A (SSTR2A). SSTR2A is a reliable biomarker of meningiomas. We report a consecutive case series of 20 patients evaluated with [68Ga]-DOTATATE PET/MRI, propose a novel approach to quantitative analysis, and discuss clinical implications., Methods: We present a consecutive case series of 20 patients with clinically suspected or pathology-proven meningioma evaluated between July 2018 and February 2019. [68Ga]-DOTATATE PET/MRI was obtained in order to confirm the diagnosis or determine tumor recurrence/progression to help guide surgical and/or radiation therapy management in cases in which MRI findings were indeterminate or equivocal., Results: Seventeen (85%) patients had undergone prior surgery and 11 (55%) underwent adjuvant radiation therapy. In 17 patients [68Ga]-DOTATATE confirmed the presence of recurrent meningioma. A total of 49 meningiomas were identified (median: 2 meningiomas/patient, range 0-14). There was excellent differentiation between meningioma and posttreatment change based on our approach of target lesion/superior sagittal sinus maximum standardized uptake values ratio (16.6 vs. 1.6, P < .0001)., Conclusions: [68Ga]-DOTATATE PET/MRI is a promising tool in the assessment of both treatment naïve and resected/irradiated meningiomas, allowing improved diagnosis and extent of disease evaluation. Future prospective studies are needed to determine utility of [68Ga]-DOTATATE PET/MRI in treatment response assessment., (© 2019 by the American Society of Neuroimaging.)

Objective: Postoperative sellar hematoma is an uncommon complication of endonasal endoscopic transsphenoidal surgery (EETS) for pituitary adenoma that often requires emergency surgical evacuation. Sellar hematomas can cause mass effect and compress parasellar structures, leading to clinically significant symptoms such as visual impairment and severe headache. The objective of this study was to determine the incidence and risk factors associated with reoperation for postoperative hematoma after EETS for pituitary adenoma., Methods: The authors reviewed a prospectively acquired database of EETS for pituitary adenoma over 13 years at Weill Cornell Medicine, NewYork-Presbyterian Hospital and identified cases that required reoperation for confirmed hematoma. They also reviewed clinical and radiographic data of a consecutive series of patients undergoing EETS for pituitary adenoma who did not have postoperative hematoma, which served as the control group. Demographic data and risk factors were compared between the groups using univariate and multivariate analyses via binary logistic regression., Results: Among a cohort of 583 patients undergoing EETS for pituitary adenoma, 9 patients (1.5%) required operation for sellar hematoma evacuation. All 9 patients with reoperation for sellar hematoma presented with worsening in their vision, and severe headache was present in 67%. New postoperative endocrine dysfunction developed in 78%. Clot evacuation improved vision in 88%. The mean time to hematoma evacuation was 4.5 days. The median length of stay for patients with sellar hematoma was 8 days (range 4-210 days) compared with a median length of stay of 3 days (range 1-32 days) for the control patients (p < 0.005). Significant risk factors in univariate analysis were tumor diameter ≥ 30 mm (p < 0.005), suprasellar extension (p < 0.005), tumor volume (p < 0.005), cavernous sinus invasion (p < 0.05), gonadotroph histology (p < 0.05), antiplatelet use (p < 0.05), and elevated BMI (p < 0.05). On multivariate analysis, tumor diameter ≥ 30 mm (OR 4.555, CI 1.30-28.90; p < 0.05) and suprasellar extension (OR 1.048, CI 1.01-1.10; p < 0.05) were found to be the only independent predictors of sellar hematoma. The incidence of hematoma in tumors ≥ 30 mm was 5% (7/139)., Conclusions: Postoperative sellar hematoma requiring reoperation is a rare phenomenon after transsphenoidal surgery, often presenting with visual loss and headache. Clot evacuation results in improvement in vision, but long-term endocrinopathy often ensues. Tumor diameter ≥ 30 mm and suprasellar extent are the most reliable risk factors. Close postoperative scrutiny should be given to patients at high risk.

Background: Patients with visual loss from macroadenomas compressing their optic apparatus may also have concomitant age-related visual pathology such as cataracts. How these two pathologies interact with each other is not well documented., Objective: The interaction between these two pathologies in elderly patients is the subject of this study., Methods: We identified a series of non-functioning macroadenoma patients over age 50 years with tumors compressing the chiasm who underwent transsphenoidal surgery at our institution between 2004 and 2018. Pre- and post-operative visual complaints, tumor size and extent of resection were analyzed. Prevalence of the diagnosis of cataract and prevalence of cataract surgery in each decade were compared with national averages., Results: We identified 200 patients who met selection criteria. 18% of these patients had a diagnosis of cataract and 12.5% had cataract surgery. Compared with the Eye Diseases Prevalence Research Group (EDPRG) study, the prevalence of cataract surgery was 2.5 times the national average of 5.1%. 32% of these patients had no improvement in their vision after cataract surgery but 76% improved after transsphenoidal surgery., Conclusions: We reported a high prevalence of cataract surgery in patients over age 50 in patients with pituitary macroadenomas compressing the optic pathway compared with national averages in patients without adenomas. While visual loss from adenoma likely precipitated more cataract surgeries in this group of patients, some who may not have required it, those patients with cataracts who did not have their cataracts extracted were less likely to recover vision after transsphenoidal surgery. Addressing both pathologies is beneficial.

Germ cell tumors are rare malignant tumors frequently located in the suprasellar region. Definitive treatment is chemotherapy and radiation. However, in some circumstances, surgery is indicated for biopsy or resection. There are limited reports of the role of the endonasal endoscopic approach (EEA) in the management of this tumor. We present two cases in which EEA was utilized for successful management of germ cell tumor. The most challenging aspect of germ cell tumor management for the treating physician is knowing the proper indications for surgery. In this paper, we highlight two specific instances, namely diagnosis and tumor refractory to chemoradiation. Given the suprasellar location, EEA is an ideal approach.

Background: Intraoperative magnetic resonance imaging (iMRI) is a technology that may improve rates of gross total resection (GTR) for pituitary adenomas. The endoscope is another less expensive technology, which also may maximize resection rates. A direct comparison of these approaches and their additive benefit has never been performed., Methods: A systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) standard. PubMed and Embase databases were searched for studies that examined GTR for pituitary adenoma resection with either endoscopic transsphenoidal surgery (eTSS), microscopic transsphenoidal surgery with iMRI (mTSS + iMRI), or endoscopic transsphenoidal surgery with iMRI (eTSS + iMRI)., Results: Eighty-five studies that reported GTR rates in 7124 pituitary adenoma patients were identified. For all pituitary adenomas, eTSS had a pooled proportion of GTR of 68.9% (95% CI 64.7-73.0%) which was similar to that of mTSS + iMRI (GTR 68.3%; 95% CI = 59.4-76.5%) and eTSS + iMRI (GTR 70.7%; 95% CI = 56.9-89.6%). For the subgroup of pituitary macroadenomas, pooled proportions for GTR were similar between eTSS and mTSS + iMRI (eTSS: GTR 59.4%; 95% CI = 49.6-68.7% vs mTSS + iMRI: GTR 68.8%; 95% CI = 57.3-79.3%), and higher for eTSS + iMRI (81.1%; 95% CI = 75.5-86.2%). The post-operative CSF leak proportion for eTSS (4.7%; 95% CI = 3.6-5.9%) was similar to that for eTSS + iMRI (3.7%; 95% CI = 1.6-6.5%) and mTSS + iMRI (4.6%; 95% CI = 2.0-8.3%). No direct statistical comparisons could be performed., Conclusion: Final GTR proportions are similar whether the surgeon uses a microscope supplemented with iMRI or endoscope with or without iMRI. The benefit of the two technologies may be complementary for macroadenomas. These findings are important to consider when comparing the efficacy of different technical strategies in the management of pituitary adenomas.

As our surgical, radiation, chemotherapeutic and supportive therapies for brain malignancies improve, and overall survival is prolonged, appropriate symptom management in this patient population becomes increasingly important. This review summarizes the published literature and current practice patterns regarding prophylactic and perioperative anti-epileptic drug use. As a wide range of anti-epileptic drugs is now available to providers, evidence guiding appropriate anticonvulsant choice is reviewed. A particular focus of this article is radiation therapy for brain malignancies. Toxicities and seizure risk associated with cranial irradiation will be discussed. Epilepsy management in patients undergoing radiation for gliomas, glioblastoma multiforme, and brain metastases will be addressed. An emerging but inconsistent body of evidence, reviewed here, indicates that anti-epileptic medications may increase radiosensitivity, and therefore improve clinical outcomes, specifically in glioblastoma multiforme patients., (Copyright © 2019 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

Recent evidence shows that seizures propagate primarily through supragranular cortical layers. To selectively modify these circuits, we developed a new technique using tightly focused, femtosecond infrared laser pulses to make as small as ~100 µm-wide subsurface cortical incisions surrounding an epileptic focus. We use this "laser scalpel" to produce subsurface cortical incisions selectively to supragranular layers surrounding an epileptic focus in an acute rodent seizure model. Compared with sham animals, these microtransections completely blocked seizure initiation and propagation in 1/3 of all animals. In the remaining animals, seizure frequency was reduced by 2/3 and seizure propagation reduced by 1/3. In those seizures that still propagated, it was delayed and reduced in amplitude. When the recording electrode was inside the partially isolated cube and the seizure focus was on the outside, the results were even more striking. In spite of these microtransections, somatosensory responses to tail stimulation were maintained but with reduced amplitude. Our data show that just a single enclosing wall of laser cuts limited to supragranular layers led to a significant reduction in seizure initiation and propagation with preserved cortical function. Modification of this concept may be a useful treatment for human epilepsy., (© The Author(s) 2018. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Background: Endoscopic skull-base surgery (ESBS) is employed in the management of diverse skull-base pathologies. Paralleling the increased utilization of ESBS, the literature in this field has expanded rapidly. However, the rarity of these diseases, the inherent challenges of surgical studies, and the continued learning curve in ESBS have resulted in significant variability in the quality of the literature. To consolidate and critically appraise the available literature, experts in skull-base surgery have produced the International Consensus Statement on Endoscopic Skull-Base Surgery (ICAR:ESBS)., Methods: Using previously described methodology, topics spanning the breadth of ESBS were identified and assigned a literature review, evidence-based review or evidence-based review with recommendations format. Subsequently, each topic was written and then reviewed by skull-base surgeons in both neurosurgery and otolaryngology. Following this iterative review process, the ICAR:ESBS document was synthesized and reviewed by all authors for consensus., Results: The ICAR:ESBS document addresses the role of ESBS in primary cerebrospinal fluid (CSF) rhinorrhea, intradural tumors, benign skull-base and orbital pathology, sinonasal malignancies, and clival lesions. Additionally, specific challenges in ESBS including endoscopic reconstruction and complication management were evaluated., Conclusion: A critical review of the literature in ESBS demonstrates at least the equivalency of ESBS with alternative approaches in pathologies such as CSF rhinorrhea and pituitary adenoma as well as improved reconstructive techniques in reducing CSF leaks. Evidence-based recommendations are limited in other pathologies and these significant knowledge gaps call upon the skull-base community to embrace these opportunities and collaboratively address these shortcomings., (© 2019 ARS-AAOA, LLC.)

Checkpoint immunotherapy (CIT) is an emerging and exciting treatment modality for the treatment of cancer. Much excitement has ensued in the potential of CIT to revolutionize the treatment and prognosis of brain metastases. The combination of stereotactic radiosurgery (SRS) and CIT has also been studied and showed promise compared with either treatment modality alone. However, several questions have arisen, in particular, the timing at which SRS and CIT should be administered relative to each other. We reviewed the reported data and attempted to offer a potential answer to this question., (Copyright © 2019 Elsevier Inc. All rights reserved.)

OBJECTIVEThere is a need for advanced imaging biomarkers to improve radiation treatment planning and response assessment. T1-weighted dynamic contrast-enhanced perfusion MRI (DCE MRI) allows quantitative assessment of tissue perfusion and blood-brain barrier dysfunction and has entered clinical practice in the management of primary and secondary brain neoplasms. The authors sought to retrospectively investigate DCE MRI parameters in meningiomas treated with resection and adjuvant radiation therapy using volumetric segmentation.METHODSA retrospective review of more than 300 patients with meningiomas resected between January 2015 and December 2018 identified 14 eligible patients with 18 meningiomas who underwent resection and adjuvant radiotherapy. Patients were excluded if they did not undergo adjuvant radiation therapy or DCE MRI. Demographic and clinical characteristics were obtained and compared to DCE perfusion metrics, including mean plasma volume (vp), extracellular volume (ve), volume transfer constant (Ktrans), rate constant (kep), and wash-in rate of contrast into the tissue, which were derived from volumetric analysis of the enhancing volumes of interest.RESULTSThe mean patient age was 64 years (range 49-86 years), and 50% of patients (7/14) were female. The average tumor volume was 8.07 cm3 (range 0.21-27.89 cm3). The median Ki-67 in the cohort was 15%. When stratified by median Ki-67, patients with Ki-67 greater than 15% had lower median vp (0.02 vs 0.10, p = 0.002), and lower median wash-in rate (1.27 vs 4.08 sec-1, p = 0.04) than patients with Ki-67 of 15% or below. Logistic regression analysis demonstrated a statistically significant, moderate positive correlation between ve and time to progression (r = 0.49, p < 0.05). Furthermore, there was a moderate positive correlation between Ktrans and time to progression, which approached, but did not reach, statistical significance (r = 0.48, p = 0.05).CONCLUSIONSThis study demonstrates a potential role for DCE MRI in the preoperative characterization and stratification of meningiomas, laying the foundation for future prospective studies incorporating DCE as a biomarker in meningioma diagnosis and treatment planning.

Minimally invasive surgical approaches for the treatment of spinal pathologies have accelerated over the past three decades and resulted in superior functional outcomes with less complications. Yet cervical pathologies have been slower to gain traction for multiple anatomical factors and its "high-risk" profile. Various minimally invasive techniques for cervical disease have now been described and validated in long-term studies with comparable outcomes to traditional open approaches and concomitant reduction in morbidity and socioeconomic costs. Transnasal operations can be used to treat ventral upper cervical disease, circumventing traditional and morbid transoral approaches. Posterior-based focused treatments for radiculopathy and myelopathy such as tubular-guided foraminotomies and unilateral laminotomies for bilateral cord decompression have also been described and becoming increasingly less invasive. Cervical fusions can now be performed percutaneously through modified, stand-alone facet joint cages that can be packed with allogeneic bone graft. These advances have been facilitated by the development of intraoperative imaging technologies (intraoperative CT) and 3-dimensional stereotactic navigation software. While this review focuses on these procedures and evidence-based outcomes data, the future for MIS applications in cervical spine surgery will continue to evolve over the coming years with wider indications and technological adjuncts., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare.

Objectives: The utilization of the nasoseptal flap (NSF) in endoscopic anterior skull base surgery (EASB) has resulted in reduced rates of postoperative cerebrospinal fluid leak (CSF). The long-term impact on sinonasal function after surgery remains incompletely defined., Methods: A consecutive series of patients undergoing EASB with NSF and with at least 3 years follow-up was prospectively evaluated. Patient demographics, pre- and postoperative Sino-nasal Outcome Test-22 (SNOT-22) scores, Lund-Mackay scores (LMS), CSF leak, and sinonasal complications were analyzed., Results: A total of 46 patients undergoing EASB with NSF met inclusion criteria. The mean follow-up was 67.4 months (range 39-90, standard deviation [SD] 14.2 months). No statistically significant differences were noted between the mean overall pre- (16) and postoperative SNOT-22 scores (18). SNOT-22 scores improved in 27 patients (58.7%), deteriorated in 17 patients (37.0%) and stayed the same in two patients (4.3%). Deterioration in SNOT-22 scores was greater in younger (mean change + 7.2 [SD17.4] vs. older patients -3.4 [SD 7.5], P = 0.010). A statistically significant increase in LMS was noted (mean preoperative LMS0.9 vs. mean postoperative LMS 2.2, P = 0.001). The LMS decreased in nine patients (19.6%), increased in 22 patients (47.8%), and remained the same in 15 patients (32.6%). One patient (2.2%) developed a postoperative CSF leak following resection of metastatic skull base lesion and was successfully treated with placement of a lumbar drain, Foley catheter balloon, and strict bed rest. One patient (2.2%) developed a postoperative mucocele requiring decompression 3 years after initial surgery., Conclusion: Whereas long-term sinonasal quality of life is overall improved in the majority of patients following NSF use for EASB, younger patients show higher incidence of deterioration. Increased sinus opacification on imaging is generally noted and may require continued follow-up and management. The incidence of reoperation for symptomatic mucocele formation is low., Level of Evidence: 4 Laryngoscope, 129:1035-1040, 2019., (© 2018 The American Laryngological, Rhinological and Otological Society, Inc.)

Brain metastases occur in a large portion of patients with cancer. Although advances in radiotherapy have helped to improve survival, they have also raised questions regarding the best modality for retreatment in the context of recurrent disease. The spectrum of treatment options for recurrent intracranial metastatic disease after previous radiotherapy includes salvage stereotactic radiosurgery, whole brain radiotherapy, and brachytherapy. We have comprehensively reviewed the existing data on the efficacy and toxicity of the various reirradiation treatment modalities. We examined the key clinical considerations that guide patient selection, such as dose, tumor size, interval to retreatment, and local control and survival rates., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Brain metastases are the most common intracranial malignancies in adults. Surgical resection is the preferred treatment approach when a pathological diagnosis is required, for symptomatic patients who are refractory to steroids, and to decompress lesions causing mass effect. Radiotherapy is administered to improve local control rates after surgical resection. After a brief review of the literature describing the treatment of brain metastases using whole-brain radiotherapy, postoperative stereotactic radiosurgery, preoperative radiosurgery, and brachytherapy, we compare patient-related, technical, practical, and radiobiological considerations of each technique. Finally, we focus our discussion on intraoperative brachytherapy, with an emphasis on the technical aspects, benefits, efficacy, and outcomes of studies utilizing permanent Cs-131 implants., (Copyright © 2019 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)

Background: Endoscopic skull base surgery has evolved over the last several decades due to technological advances and operative techniques. Several innovations that are not yet mainstream may have significant impact on the future of endoscopic skull base surgery., Methods: Current literature pertaining to innovations in endoscopic skull base surgery was retrieved using PubMed, Embase, Web of Science, and Google Scholar., Results: Several recent innovations may play an influential role in the advancement of endoscopic skull base surgery, including fluorescent dyes such as indocyanine green fluorescence, fluorescein, and 5-aminolevulinic acid, 3-dimensional endoscopes, robotic surgery, and intraoperative magnetic resonance imaging., Conclusions: Several technologies are under current investigation with the hope to improve future outcomes in endoscopic skull base surgery. Additional research and evolution are necessary and will require intense scrutiny before becoming standard of care., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Endonasal endoscopic approaches (EEA) to the third ventricle are well described but generally use an infrachiasmatic route since the suprachiasmatic translamina terminalis corridor is blocked by the anterior communicating artery (AComA). The bifrontal basal interhemispheric translamina terminalis approach has been facilitated with transection of the AComA. The aim of the study is to describe the anatomical feasibility and limitations of the EEA translamina terminalis approach to the third ventricle augmented with AComA surgical ligation., Methods: Endoscopic dissections were performed on five cadaveric heads injected with colored latex using rod lens endoscopes attached to a high-definition camera and a digital video recorder system. A stepwise anatomical dissection of the endoscopic endonasal transtuberculum, transplanum, translamina terminalis approach to the third ventricle was performed. Measurements were performed before and after AComA elevation and transection using a millimeter flexible caliper., Results: Multiple comparison statistical analysis revealed a statistically significant difference in vertical exposure between the control condition and after AComA elevation, between the control condition and after AComA division and between the AComA elevation and division (p < 0.05). The mean difference in exposed surgical area was statistically significant between the control and after AComA division and between elevation and AComA division (p < 0.01), whereas it was not statistically significant between the control condition and AComA elevation (NS)., Conclusion: The anatomical feasibility of clipping and dividing the AComA through an EEA has been demonstrated in all the cadaveric specimens. The approach facilitates exposure of the suprachiasmatic optic recess within the third ventricle that may be a blind spot during an infrachiasmatic approach.