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The purpose of this report is to chronicle a 2-decade period of educational innovation and improvement, as well as governance reform, across the specialty of neurological surgery. Neurological surgery educational and professional governance systems have evolved substantially over the past 2 decades with the goal of improving training outcomes, patient safety, and the quality of US neurosurgical care. Innovations during this period have included the following: creating a consensus national curriculum; standardizing the length and structure of neurosurgical training; introducing educational outcomes milestones and required case minimums; establishing national skills, safety, and professionalism courses; systematically accrediting subspecialty fellowships; expanding professional development for educators; promoting training in research; and coordinating policy and strategy through the cooperation of national stakeholder organizations. A series of education summits held between 2007 and 2009 restructured some aspects of neurosurgical residency training. Since 2010, ongoing meetings of the One Neurosurgery Summit have provided strategic coordination for specialty definition, neurosurgical education, public policy, and governance. The Summit now includes leadership representatives from the Society of Neurological Surgeons, the American Association of Neurological Surgeons, the Congress of Neurological Surgeons, the American Board of Neurological Surgery, the Review Committee for Neurological Surgery of the Accreditation Council for Graduate Medical Education, the American Academy of Neurological Surgery, and the AANS/CNS Joint Washington Committee. Together, these organizations have increased the effectiveness and efficiency of the specialty of neurosurgery in advancing educational best practices, aligning policymaking, and coordinating strategic planning in order to meet the highest standards of professionalism and promote public health.

Surgeon providers and billing professionals use Current Procedural Terminology (CPT) codes to specify patient treatment and associated charges. In the present study, coding discrepancies between surgeons' first pass coding and employed coders' final codes were investigated. A total of 500 patients over 3 months were retrospectively analyzed for coding discrepancies. To quantify the impact of change, codes with the most accumulated discrepancies were studied and change to annual relative value unit (RVU) was determined. Final submission of codes to billing demonstrated a 161% increase in total codes by the professional coders, versus original surgeon-derived codes (1594 vs 987 CPT codes). The most common source of change between the surgeon and coder was the addition of distinct codes by the billing professional (270 patients, 54.51%). These results demonstrate the existence of coding discrepancies. Future investigation will evaluate the communication between surgeons and billing professionals.

OBJECTIVE To characterize the patient and clinical factors that determine variability in hospital costs following endoscopic transphenoidal pituitary surgery. METHODS All endoscopic transphenoidal pituitary surgeries performed from January 1, 2015, to October 24, 2017, with complete data were evaluated in this retrospective single-institution study. The electronic medical record was reviewed for patient factors, tumor characteristics, and cost variables during each hospital stay. Multivariate linear regression was performed using Stata software. RESULTS The analysis included 190 patients and average length of stay was 4.71 days. Average total in-hospital cost was $28,624 (95% confidence interval $25,094-$32,155) with average total direct cost of $19,444 ($17,136-$21,752) and total indirect cost of $9181 ($7592-$10,409). On multivariate regression, post-operative cerebrospinal fluid (CSF) leak was associated with a significant increase in all cost variables, including a total cost increase of $40,981 ($15,474-$66,489, P = .002). Current smoking status was associated with an increased total cost of $20,189 ($6,638-$33,740, P = .004). Self-reported Caucasian ethnicity was associated with a significant decrease in total cost of $6646 (-$12,760 to -$532, P = .033). Post-operative DI was associated with increased costs across all variables that were not statistically significant. CONCLUSIONS Post-operative CSF leak, current smoking status, and non-Caucasian ethnicity were associated with significantly increased costs. Understanding of cost drivers of endoscopic transphenoidal pituitary surgery is critical for future cost control and value creation initiatives. LEVEL OF EVIDENCE 3 Laryngoscope, 131:760-764, 2021.

OBJECTIVEMultidisciplinary treatment including medical oncology, radiation oncology, and surgical consultation is necessary to provide comprehensive therapy for patients with spinal metastases. The goal of this study was to review the use of radiation therapy and/or surgical intervention and their impact on patient outcomes.METHODSIn this retrospective series, the authors identified at their institution those patients with spinal metastases who had received radiation therapy alone or had undergone surgery with or without radiation therapy within a 6-year period. Data on patient age, chemotherapy, surgical procedure, radiation therapy, Karnofsky Performance Status (KPS), primary tumor pathology, Spinal Instability Neoplastic Score (SINS), and survival after treatment were collected from the patient electronic medical records. N − 1 chi-square testing was used for comparisons of proportions. The Student t-test was used for comparisons of means. A p value < 0.05 was considered statistically significant. A survival analysis was completed using a multivariate Cox proportional hazards model.RESULTSTwo hundred thirty patients with spinal metastases were identified, 109 of whom had undergone surgery with or without radiation therapy. Among the 104 patients for whom the surgical details were reviewed, 34 (33%) had a history of preoperative radiation to the surgical site but ultimately required surgical intervention. In this surgical group, a significantly increased frequency of death within 30 days was noted for the SINS unstable patients (23.5%) as compared to that for the SINS stable patients (2.3%; p < 0.001). The SINS was a significant predictor of time to death among surgical patients (HR 1.11, p = 0.037). Preoperative KPS was not independently associated with decreased survival (p > 0.5) on univariate analysis. One hundred twenty-six patients met the criteria for inclusion in the radiation-only analysis. Ninety-eight of these patients (78%) met the criteria for potential instability (PI) at the time of treatment, according to the SINS system. Five patients (5%) with PI in the radiation therapy group had a documented neurosurgical or orthopedic surgery consultation prior to radiation therapy.CONCLUSIONSAt the authors’ institution, patients with gross mechanical instability per the SINS system had an increased rate of 30-day postoperative mortality, which remained significant when controlling for other factors. Surgical consultation for metastatic spine patients receiving radiation oncology consultation with PI is low. The authors describe an institutional pathway to encourage multidisciplinary treatment from the initial encounter in the emergency department to expedite surgical evaluation and collaboration.

OBJECTIVEAlthough it is known that intersurgeon variability in offering elective surgery can have major consequences for patient morbidity and healthcare spending, data addressing variability within neurosurgery are scarce. The authors performed a prospective peer review study of randomly selected neurosurgery cases in order to assess the extent of consensus regarding the decision to offer elective surgery among attending neurosurgeons across one large academic institution.METHODSAll consecutive patients who had undergone standard inpatient surgical interventions of 1 of 4 types (craniotomy for tumor [CFT], nonacute redo CFT, first-time spine surgery with/without instrumentation, and nonacute redo spine surgery with/without instrumentation) during the period 2015–2017 were retrospectively enrolled (n = 9156 patient surgeries, n = 80 randomly selected individual cases, n = 20 index cases of each type randomly selected for review). The selected cases were scored by attending neurosurgeons using a need for surgery (NFS) score based on clinical data (patient demographics, preoperative notes, radiology reports, and operative notes; n = 616 independent case reviews). Attending neurosurgeon reviewers were blinded as to performing provider and surgical outcome. Aggregate NFS scores across various categories were measured. The authors employed a repeated-measures mixed ANOVA model with autoregressive variance structure to compute omnibus statistical tests across the various surgery types. Interrater reliability (IRR) was measured using Cohen’s kappa based on binary NFS scores.RESULTSOverall, the authors found that most of the neurosurgical procedures studied were rated as “indicated” by blinded attending neurosurgeons (mean NFS = 88.3, all p values < 0.001) with greater agreement among neurosurgeon raters than expected by chance (IRR = 81.78%, p = 0.016). Redo surgery had lower NFS scores and IRR scores than first-time surgery, both for craniotomy and spine surgery (ANOVA, all p values < 0.01). Spine surgeries with fusion had lower NFS scores than spine surgeries without fusion procedures (p < 0.01).CONCLUSIONSThere was general agreement among neurosurgeons in terms of indication for surgery; however, revision surgery of all types and spine surgery with fusion procedures had the lowest amount of decision consensus. These results should guide efforts aimed at reducing unnecessary variability in surgical practice with the goal of effective allocation of healthcare resources to advance the value paradigm in neurosurgery.

Introduction Vancomycin may be used as an alternative perioperative antibiotic for penicillin-allergic patients but follows a different infusion timing. At the institution presented herein, noncompliance with recommended vancomycin infusion timing has been hypothesized to contribute toward increased risk of surgical site infections and avoidable expenditures. The objective of this project was to utilize the Performance Improvement In Action methodology to identify, address, and solve the problem of vancomycin administration timing. Methodology This study took place at a multi-hospital, urban academic medical center. The protocol was developed by neurosurgery and anesthesia faculty, advanced practice providers, nursing, and pharmacy. Timing of the following points was recorded: initial order, order release, pharmacy verification, vancomycin infusion, and surgical incision. Fifty consecutive penicillin-allergic patients undergoing neurosurgical intervention were prospectively enrolled. Data comparison was made between the pilot and retrospective review cohorts. Results The pilot cohort achieved correct administration of vancomycin in 100% of cases. Average infusion start time prior to incision increased by 257% (p

OBJECTIVEIntraoperative molecular imaging with tumor-targeted fluorescent dyes can enhance resection rates. In contrast to visible-light fluorophores (e.g., 5-aminolevulinic-acid), near-infrared (NIR) fluorophores have increased photon tissue penetration and less contamination from tissue autofluorescence. The second-window ICG (SWIG) technique relies on passive accumulation of indocyanine green (ICG) in neoplastic tissues. OTL38, conversely, targets folate receptor overexpression in nonfunctioning pituitary adenomas. In this study, we compare the properties of these 2 modalities for NIR imaging of pituitary adenomas to better understand the potential for NIR imaging in neurosurgery.METHODSA total of 39 patients with pituitary adenomas were enrolled between June 2015 and January 2018 in 2, sequential, IRB-approved studies. Sixteen patients received systemic ICG infusions 24 hours prior to surgery, and another 23 patients received OTL38 infusions 2–3 hours prior to surgery. NIR fluorescence signal-to-background ratio (SBR) was recorded during and after resection. Immunohistochemistry was performed on the 23 adenomas resected from patients who received OTL38 to assess expression of folate receptor–alpha (FRα).RESULTSAll 16 adenomas operated on after ICG administration demonstrated strong NIR fluorescence (mean SBR 4.1 ± 0.69 [SD]). There was no statistically significant difference between the 9 functioning and 7 nonfunctioning adenomas (p = 0.9). After administration of OTL38, the mean SBR was 1.7 ± 0.47 for functioning adenomas, 2.6 ± 0.91 for all nonfunctioning adenomas, and 3.2 ± 0.53 for the subset of FRα-overexpressing adenomas. Tissue identification with white light alone for all adenomas demonstrated 88% sensitivity and 90% specificity. SWIG demonstrated 100% sensitivity but only 29% specificity for both functioning and nonfunctioning adenomas. OTL38 was 75% sensitive and 100% specific for all nonfunctioning adenomas, but when assessment was limited to the 9 FRα-overexpressing adenomas, the sensitivity and specificity of OTL38 were both 100%.CONCLUSIONSIntraoperative imaging with NIR fluorophores demonstrates highly sensitive detection of pituitary adenomas. OTL38, a folate-receptor–targeted fluorophore, is highly specific for nonfunctioning adenomas but has no utility in functioning adenomas. SWIG, which relies on passive diffusion into neoplastic tissue, is applicable to both functioning and nonfunctioning pituitary adenomas, but it is less specific than targeted fluorophores. Thus, targeted and nontargeted NIR fluorophores play important, yet distinct, roles in intraoperative imaging. Selectively and intelligently using either agent has the potential to greatly improve resection rates and outcomes for patients with intracranial tumors.

Objective Chronic rhinosinusitis (CRS) is a proposed risk factor for meningitis and other intracranial complications following the endoscopic endonasal transsphenoidal approach (TSA). Some have recommended staging TSA following surgery for CRS; however, delaying TSA has important ramifications. The objective of this study is to determine whether asymptomatic sinonasal inflammation (RSNI) on preoperative computed tomography scans, without clinical CRS, is associated with postoperative complications following TSA. Methods All consecutive TSA cases performed at a single tertiary care institution from January 1, 2009, to December 31, 2017, were reviewed for patient demographics, prior surgery, presence of RSNI on preoperative computed tomography scan based on Lund-Mackay (LM) score, intraoperative cerebrospinal fluid (CSF) leak, and postoperative complications (postoperative CSF leak, bleeding, infection). The association between preoperative RSNI and postoperative complications was analyzed via multivariate logistic regression. Results One hundred seventy-one cases of TSA were included with mean patient age of 52.6 years, 42.7% males, 18.1% revision cases, and mean LM score of 1.9 ± 2.7. Complications were identified in 9.9% of patients at the following rates: 5.3% postoperative CSF leak, 2.9% bleeding, and 1.8% infection (all sinusitis, no episodes of meningitis). Neither total LM score nor LM score > 5 (representative of clinically significant radiographic CRS) were predictors of any postoperative complication (both P > 0.05). Age, sex, revision status, intraoperative CSF leak, and total LM score were not independent predictors of any postoperative complication on multivariate analysis (all P > 0.05). Conclusion In asymptomatic patients, radiographic evidence of sinonasal inflammation is not associated with increased risk of complications following TSA. Level of evidence 4 Laryngoscope, 129:1545-1548, 2019.

Background: Early, high-quality advance care planning discussions are essential for supporting goal-concordant care among glioblastoma (GBM) patients. Objective: Using mixed methods, we sought to characterize current serious illness (SI) communication practices at our institution. Methods: The electronic medical records of 240 deceased GBM patients cared for at the Abramson Cancer Center in Philadelphia, PA between 2017 and 2019 were systematically reviewed for documented SI conversations about four domains: prognosis, goals, end-of-life planning, and code status. Patient outcomes and SI conversation characteristics were analyzed using descriptive statistics. Standardized interviews about GBM care were held with five clinicians. Interview transcripts were analyzed using grounded-theory coding to identify emergent themes. Results: Nearly all patients (96%) had at least one documented SI conversation (median: 4, interquartile range [IQR] 2-7), mostly outpatient with medical oncology physicians. Median timing of first SI conversation was 360 days before death. SI conversations were not significantly associated with patient outcomes, including inpatient death and hospice enrollment. Seven themes emerged from clinician interviews: balancing hope and reality, anticipatory guidance, neglect of the "big picture," need for earlier conversations, care coordination, the role of clinical expertise, and communication training. Conclusion: SI conversations were documented early and often in our sample, but their quality was difficult to assess. Contrary to our quantitative findings, interviewees reported that SI conversations were late, infrequent, inadequate, and fragmented across specialties, failing to explore critical issues such as prognosis and functional decline.

OBJECTIVEWith nearly half of graduating US medical students being female, it is imperative to understand why females typically make up less than 20% of the neurosurgery applicant pool, a number that has changed very slowly over the past several decades. Organized neurosurgery has strongly indicated the desire to overcome the underrepresentation of women, and it is critical to explore whether females are at a disadvantage during the residency application process, one of the first steps in a neurosurgical career. To date, there are no published studies on specific applicant characteristics, including gender, that are associated with match outcome among neurosurgery resident applicants. The purpose of this study is to determine which characteristics of neurosurgery residency applicants, including gender, are associated with a successful match outcome.METHODSDe-identified neurosurgical resident applicant data obtained from the San Francisco Fellowship and Residency Matching Service for the years 1990–2007 were analyzed. Applicant characteristics including gender, medical school attended, year of application, United States Medical Licensing Exam (USMLE) Step 1 score, Alpha Omega Alpha (AOA) status, and match outcome were available for study.RESULTSOf the total 3426 applicants studied, 473 (13.8%) applicants were female and 2953 (86.2%) were male. Two thousand four hundred forty-eight (71.5%) applicants successfully matched. USMLE Step 1 score was the strongest predictor of match outcome with scores > 245 having an OR of 20.84 (95% CI 10.31–42.12) compared with those scoring < 215. The mean USMLE Step 1 score for applicants who successfully matched was 233.2 and was 210.8 for those applicants who did not match (p < 0.001). Medical school rank was also associated with match outcome (p < 0.001). AOA status was not significantly associated with match outcome. Female gender was associated with significantly lower odds of matching in both simple (OR 0.59, 95% CI 0.48–0.72) and multivariate analyses (OR 0.57, 95% CI 0.34–0.94 CI). USMLE Step 1 scores were significantly lower for females compared to males with a mean score of 230.1 for males and 221.5 for females (p < 0.001). There was no significant difference in medical school ranking or AOA status when stratified by applicant gender.CONCLUSIONSThe limited historical applicant data from 1990–2007 suggests that USMLE Step 1 score is the best predictor of match outcome, although applicant gender may also play a role.

BACKGROUND Bundled care payments are increasingly being explored for neurosurgical interventions. In this setting, skilled nursing facility (SNF) is less desirable from a cost perspective than discharge to home, underscoring the need for better preoperative prediction of postoperative disposition. OBJECTIVE To assess the capability of the Risk Assessment and Prediction Tool (RAPT) and other preoperative variables to determine expected disposition prior to surgery in a heterogeneous neurosurgical cohort, through observational study. METHODS Patients aged 50 yr or more undergoing elective neurosurgery were enrolled from June 2016 to February 2017 (n = 623). Logistic regression was used to identify preoperative characteristics predictive of discharge disposition. Results from multivariate analysis were used to create novel grading scales for the prediction of discharge disposition that were subsequently compared to the RAPT Score using Receiver Operating Characteristic analysis. RESULTS Higher RAPT Score significantly predicted home disposition (P

BACKGROUND: Surgical resection is the primary treatment for nonfunctional (NF) pituitary adenomas, but gross-total resection is difficult to achieve in all cases. NF adenomas overexpress folate receptor alpha (FRα). OBJECTIVE: To test the hypothesis that we could target FRα for highly sensitive and specific intraoperative detection of NF adenomas using near-infrared (NIR) imaging. METHODS: Fourteen patients with NF pituitary adenoma were infused with the folate analog NIR dye OTL38 preoperatively. NIR fluorescence signal-to-background ratio (SBR) was recorded for each tumor during resection of the adenomas. Extent of surgery was not modified based on the presence or absence of fluorescence. Immunohistochemistry was performed to assess FRα expression in all specimens. Magnetic resonance imaging (MRI) was performed postoperatively to assess residual neoplasm. RESULTS: Nine adenomas overexpressed FRα and fluoresced with a NIR SBR of 3.2 ± 0.52, whereas the 5 non-FRα-overexpressing adenomas fluoresced with an SBR of 1.5 ± 0.21. Linear regression demonstrated a significant correlation between intraoperative SBR and the FRα expression (P-value

Objective The goal of this study is to provide a clinical pathway for shunt valve adjustment in the treatment of normal pressure hydrocephalus (NPH) patients. Patient and methods The authors conducted a single-center retrospective study of 102 patients (mean age 74 years, 66 men, 36 women) diagnosed with NPH. In all cases, a Medtronic Strata Adjustable Pressure valve set initially at 1.5 was implanted. Outcome was based on the clinical status of the patient at the last contact point with the senior author. Patients were adjusted with reductions or increases of 0.5 per follow-up visit to achieve the best clinical outcome and avoid complications. Complications were categorized as infection, shunt malfunction, subdural hygroma/hematoma, or any adverse event able to be attributed to a change in shunt setting or surgical procedure. Results Of the 102 patients, 60% had the triad of clinical symptoms, 5% had gait dysfunction only, 2% had dementia only, 4% had urine incontinence and gait dysfunction, 1% had urine incontinence and dementia, and 28% had gait dysfunction and dementia. Over a mean clinical follow-up of 19 months, 71 patients had improvement or resolution of NPH symptoms at the last point of contact with the senior author. Of the 71 patients, 24% improved in all 3 symptoms, 8% improved in urine incontinence only, 17% improved in gait dysfunction only, 15% improved in dementia only, 15% improved in urine incontinence and gait dysfunction only, 4% improved in urine incontinence and dementia only, and 15% improved in gait dysfunction and dementia only. Valve pressure adjustment was required at least once in 85 patients (mean number of 1.68 adjustments, 7 maximum); 10% had 0.5 as the final setting, 47% had 1.0 as the final setting, 36% had 1.5 as the final setting, 7% had 2.0 as the final setting, and 0% had 2.5 as the final setting. There were 41 (40%) complications overall: 28 subdural hygromas/hematomas, of which 5 required surgical evacuation; 9 distal obstructions requiring surgical revision; 4 seizures; 2 infections; 1 exposed shunt tubing; 1 intraparenchymal hematoma of unknown etiology. Conclusion Standardization of post-operative care for patients with NPH is possible. The present manuscript offers a safe and effective pathway for treatment of NPH patients with the Strata Adjustable Pressure Valve.

BACKGROUND Patients with an external ventricular drain (EVD) may not be readily mobilized because of concerns of catheter dislodgment and/or inappropriate cerebrospinal fluid drainage. Delayed mobilization may result in longer hospital stays and an increased risk for complications related to immobility. We aimed to determine the safety, feasibility, and outcome of an EVD mobilization protocol in patients with subarachnoid hemorrhage (SAH). METHODS A multidisciplinary group developed a formal algorithm for the mobilization of patients with SAH with EVDs. Outcome measures included intensive care unit (ICU) length of stay (LOS), day to first mobilization, and discharge disposition. Patients were prospectively enrolled during a 12-month period and compared with a historical control group of patients with SAH for the preceding 12-month period. RESULTS Thirty-nine of 45 (86.7%) patients were women. Mean age did not differ significantly between the preintervention (n = 19) and postintervention (n = 26) groups (59.6 vs 55.7). Number of EVD device days did not differ significantly between groups (16.3 vs 15, P = .422]. Of 101 attempted postintervention mobilization sessions, six were aborted for increased lethargy (1), pain (1), elevated intracranial pressure (1), drain malfunction (1), and hypotension (2). Twenty-four sessions were attempted but never initiated because of worsening neurologic examination (10), pulmonary instability (2), hemodynamic instability (2), medical instability (3), and provider request (1). No patient experienced catheter dislodgment. Mean ICU LOS was not different between groups (20.7 vs 18.2, P = .262). The day of first mobilization was significantly earlier in the postintervention group (18.7 vs 6.5, P < .0001). The percentage of patients discharged home or to acute rehabilitation was higher in the postintervention group (63.2% vs 88.5%, P = .018], when accounting for Hunt and Hess grade. CONCLUSIONS The mobilization of patients with EVDs is safe and feasible; it may be associated with earlier mobilization, reduced ICU LOS, and better discharge disposition. No major complications were attributable to early mobilization.

IMPORTANCE: United States government personnel experienced potential exposures to uncharacterized directional phenomena while serving in Havana, Cuba, from late 2016 through May 2018. The underlying neuroanatomical findings have not been described. OBJECTIVE: To examine potential differences in brain tissue volume, microstructure, and functional connectivity in government personnel compared with individuals not exposed to directional phenomena. DESIGN, SETTING, AND PARTICIPANTS: Forty government personnel (patients) who were potentially exposed and experienced neurological symptoms underwent evaluation at a US academic medical center from August 21, 2017, to June 8, 2018, including advanced structural and functional magnetic resonance imaging analytics. Findings were compared with imaging findings of 48 demographically similar healthy controls. EXPOSURES: Potential exposure to uncharacterized directional phenomena of unknown etiology, manifesting as pressure, vibration, or sound. MAIN OUTCOMES AND MEASURES: Potential imaging-based differences between patients and controls with regard to (1) white matter and gray matter total and regional brain volumes, (2) cerebellar tissue microstructure metrics (eg, mean diffusivity), and (3) functional connectivity in the visuospatial, auditory, and executive control subnetworks. RESULTS: Imaging studies were completed for 40 patients (mean age, 40.4 years; 23 [57.5%] men; imaging performed a median of 188 [range, 4-403] days after initial exposure) and 48 controls (mean age, 37.6 years; 33 [68.8%] men). Mean whole brain white matter volume was significantly smaller in patients compared with controls (patients: 542.22 cm(3); controls: 569.61 cm(3); difference, −27.39 [95% CI, −37.93 to −16.84] cm(3); P

Objective Surgical resection is widely accepted as a critical component for definitive treatment of sinonasal mucosal melanoma. Systemic immunotherapy, including multiple newer agents, has been used to treat metastatic or unresectable disease. In this study, we examine its efficacy in locoregional control when used in conjunction with surgical resection for primary mucosal lesions. Design Present study is a retrospective review of all patients at a tertiary academic medical center with primary sinonasal mucosal melanoma and distant metastatic disease. Results A total of four patients were identified. In all cases, patients were treated with a combination of surgical resection of the primary tumor and systemic immunotherapy. Three patients were initially treated with surgery at the primary site followed by immunotherapy for distant metastases. Response to immunotherapy at the sites of primary and metastatic disease was seen in two patients. All four patients developed progression or recurrence at the primary site following initiation of immunotherapy for which they underwent surgical resection. One patient remains in follow-up without evidence of disease 20 months after initial treatment; three succumbed to the disease at 135, 37, and 16 months after initial treatment. Conclusion Surgical resection for local control plays a critically important role in the treatment of sinonasal mucosal melanoma regardless of the presence of metastases and whether immunotherapy will be given. This case series suggests that, though immunotherapy may demonstrate efficacy in managing distant disease, surgery should remain the first-line treatment for the primary site.

Objective Radiation therapy represents an uncommon but important component of treatment plans for some pituitary adenomas (PAs). Although radiation therapy has been used to treat pituitary adenomas for over a century, general trends in the usage of radiation therapy for this purpose have not been reviewed. Additionally, there are few large studies evaluating how radiation therapy is used for the treatment of these benign tumors. Investigating these trends and identifying any variations in radiation therapy utilization would help to better inform treatment decisions and improve patient outcomes. Design Present study is a retrospective analysis of cases using the National Cancer Database. Setting The research was organized at a tertiary academic medical center. Participants Patients were diagnosed with pituitary adenoma between 2004 and 2014 within the National Cancer Database (NCDB). Methods Temporal trends in the usage of radiation therapy to treat pituitary adenoma were analyzed through a retrospective analysis of 77,142 pituitary adenoma cases from the NCDB between 2004 and 2014. Univariate and multivariate analyses were to examine the relationship between patient, tumor, and treatment factors, and the incorporation of radiation therapy into the treatment of pituitary adenomas. We adjusted for potential confounders such as age, sex, race, comorbidity score, facility type, and year of diagnosis. Results A total of 77,142 patients met inclusion criteria. Inclusion of radiation therapy in pituitary adenoma treatment was 8.0% in 2004 and steadily declined to a low of 3.1% in 2014. Overall, patients were less likely to receive radiation for their pituitary adenoma over time (p Conclusion In this sample of pituitary adenoma patients treated at NCDB institutions between 2004 and 2014, we found a steady decline in the incorporation of radiation therapy in treatment, as well as in the use of any type of intervention for PA treatment, suggesting a rise in noninterventional observation of PA.

This cross-sectional analysis of nationally representative hospitalizations uses data from the National Inpatient Sample and 3 national surveys of ambulatory surgery to compare the frequency of use of optic nerve sheath fenestration vs cerebrospinal fluid shunt placement for the treatment of pseudotumor cerebri syndrome., Key Points Question How often is optic nerve sheath fenestration (ONSF) used relative to cerebrospinal fluid shunting procedures to treat pseudotumor cerebri syndrome (PTCS) in the United States? Findings In a cross-sectional analysis of nationally representative hospitalization data on 10 720 surgical procedures from the National Inpatient Sample, shunting was more than 10 times more common than ONSF, and this gap has widened as shunting for PTCS increased from 2002 to 2016. However, because the overall rate of PTCS-related hospitalization has increased even more rapidly, the percentage of inpatients with PTCS undergoing surgery has decreased. Meaning This study’s findings suggest that ONSF is used less frequently than shunting for PTCS, which may reflect underlying trends in medical treatment practices and outcomes or growing limitations in access to ophthalmic surgical expertise., Importance Optic nerve sheath fenestration (ONSF) and cerebrospinal fluid shunting are sometimes used to treat pseudotumor cerebri syndrome (PTCS), but their use patterns are unknown. Objectives To investigate the frequency of surgical PTCS treatment in the United States and to compare patients undergoing ONSF with those treated with shunting. Design, Setting, and Participants This was a retrospective longitudinal cross-sectional study. Inpatient data were obtained from the National Inpatient Sample (NIS), and outpatient surgical center data were obtained from the National Survey of Ambulatory Surgery (NSAS) and National Hospital Ambulatory Medical Care Survey (NHAMCS). Included in the analysis were 10 720 patients aged 18 to 65 years with a diagnosis code for PTCS, excluding venous thrombosis and other causes of intracranial hypertension. Time trends were explored and logistic regression was used to measure differences according to age, race/ethnicity, sex, Elixhauser comorbidity index, and other patient and hospital characteristics. Data analysis was performed from March 31 to October 7, 2020. Exposure Treatment for PTCS, excluding venous thrombosis and other causes of intracranial hypertension. Main Outcomes and Measures Annual number of PTCS-related admissions, ONSFs, and shunt procedures from 2002-2016. Patient and hospital-level characteristics of patients with PTCS undergoing ONSF or shunting were compared. Results Between 2010 and 2016, 297 ONSFs were performed and 10 423 shunts were placed as treatment for PTCS. The procedures were most commonly performed in individuals aged 26 to 35 years (39.4%), and 9920 (92.4%) of the surgically treated patients were women. ONSF was more common among younger patients (eg, adjusted odds ratio [AOR] for patients ≥46 years vs those 18-25 years, 0.22; 95% CI, 0.08-0.61) and in Black, Hispanic, or other minority populations (AOR, 2.37; 95% CI, 1.31-4.30) and less common in the South (AOR, 0.34; 95% CI, 0.13-0.88) and West (AOR, 0.15; 95% CI, 0.04-0.58) compared with the Northeast. Total PTCS-related hospitalizations increased from 6081 (95% CI, 5137-7025) in 2002 to 18 020 (95% CI, 16 607-19 433) in 2016. Shunting increased from 2002 to 2011 and subsequently plateaued and declined. ONSF was used much less frequently, and use has not increased. No instances of outpatient ONSF or shunting for PTCS were recorded in the NSAS or NHAMCS databases. Conclusions and Relevance This study’s findings suggest that shunting is more common than ONSF and that the use gap has widened as shunting has increased. However, because overall PTCS-related hospitalizations have increased even more rapidly, the percentage of inpatients with PTCS undergoing surgery has decreased. These trends may reflect changes in medical treatment practices and outcomes or growing limitations in access to ophthalmic surgical expertise.

Meningiomas are the most common primary brain tumor of adults. The majority are benign (WHO grade I), with a mostly indolent course; 20% of them (WHO grade II and III) are, however, considered aggressive and require a more complex management. WHO grade II and III tumors are heterogeneous and, in some cases, can develop from a prior lower grade meningioma, although most arise de novo. Mechanisms leading to progression or implicated in de novo grade II and III tumorigenesis are poorly understood. RNA-seq was used to profile the transcriptome of grade I, II, and III meningiomas and to identify genes that may be involved in progression. Bioinformatic analyses showed that grade I meningiomas that progress to a higher grade are molecularly different from those that do not. As such, we identify GREM2, a regulator of the BMP pathway, and the snoRNAs SNORA46 and SNORA48, as being significantly reduced in meningioma progression. Additionally, our study has identified several novel fusion transcripts that are differentially present in meningiomas, with grade I tumors that did not progress presenting more fusion transcripts than all other tumors. Interestingly, our study also points to a difference in the tumor immune microenvironment that correlates with histopathological grade. Electronic supplementary material The online version of this article (10.1186/s40478-019-0690-x) contains supplementary material, which is available to authorized users.

No abstract available.

OBJECTIVEEnhanced recovery after surgery (ERAS) protocols address pre-, peri-, and postoperative factors of a patient’s surgical journey. The authors sought to assess the effects of a novel ERAS protocol on clinical outcomes for patients undergoing elective spine or peripheral nerve surgery.METHODSThe authors conducted a prospective cohort analysis comparing clinical outcomes of patients undergoing elective spine or peripheral nerve surgery after implementation of the ERAS protocol compared to a historical control cohort in a tertiary care academic medical center. Patients in the historical cohort (September–December 2016) underwent traditional surgical care. Patients in the intervention group (April–June 2017) were enrolled in a unique ERAS protocol created by the Department of Neurosurgery at the University of Pennsylvania. Primary objectives were as follows: opioid and nonopioid pain medication consumption, need for opioid use at 1 month postoperatively, and patient-reported pain scores. Secondary objectives were as follows: mobilization and ambulation status, Foley catheter use, need for straight catheterization, length of stay, need for ICU admission, discharge status, and readmission within 30 days.RESULTSA total of 201 patients underwent surgical care via an ERAS protocol and were compared to a total of 74 patients undergoing traditional perioperative care (control group). The 2 groups were similar in baseline demographics. Intravenous opioid medications postoperatively via patient-controlled analgesia was nearly eliminated in the ERAS group (0.5% vs 54.1%, p < 0.001). This change was not associated with an increase in the average or daily pain scores in the ERAS group. At 1 month following surgery, a smaller proportion of patients in the ERAS group were using opioids (38.8% vs 52.7%, p = 0.041). The ERAS group demonstrated greater mobilization on postoperative day 0 (53.4% vs 17.1%, p < 0.001) and postoperative day 1 (84.1% vs 45.7%, p < 0.001) compared to the control group. Postoperative Foley use was decreased in the ERAS group (20.4% vs 47.3%, p < 0.001) without an increase in the rate of straight catheterization (8.1% vs 11.9%, p = 0.51).CONCLUSIONSImplementation of this novel ERAS pathway safely reduces patients’ postoperative opioid requirements during hospitalization and 1 month postoperatively. ERAS results in improved postoperative mobilization and ambulation.

Neurofibromatosis types 1 (NF-1) and 2 are significant entities to otolaryngologists because they frequently involve head and neck skin, brain, skull base, orbits, and surrounding neural and vascular structures. We present the case of a 52-year-old male with progressive, marked unilateral proptosis due to a multilobulated orbital mass, secondary to biopsy-proven plexiform neurofibroma (PN). Acute worsening of proptosis leading to corneal abrasion, diplopia, and pain required debulking surgery, for which an orbitozygomatic approach was utilized. Genetic testing for NF-1 revealed no mutation. This rare case of NF-negative orbital PN and multidisciplinary treatment considerations for expansile orbital tumors are discussed.

Importance From late 2016 through August 2017, US government personnel serving on diplomatic assignment in Havana, Cuba, reported neurological symptoms associated with exposure to auditory and sensory phenomena. Objective To describe the neurological manifestations that followed exposure to an unknown energy source associated with auditory and sensory phenomena. Design, Setting, and Participants Preliminary results from a retrospective case series of US government personnel in Havana, Cuba. Following reported exposure to auditory and sensory phenomena in their homes or hotel rooms, the individuals reported a similar constellation of neurological symptoms resembling brain injury. These individuals were referred to an academic brain injury center for multidisciplinary evaluation and treatment. Exposures Report of experiencing audible and sensory phenomena emanating from a distinct direction (directional phenomena) associated with an undetermined source, while serving on US government assignments in Havana, Cuba, since 2016. Main Outcomes and Measures Descriptions of the exposures and symptoms were obtained from medical record review of multidisciplinary clinical interviews and examinations. Additional objective assessments included clinical tests of vestibular (dynamic and static balance, vestibulo-ocular reflex testing, caloric testing), oculomotor (measurement of convergence, saccadic, and smooth pursuit eye movements), cognitive (comprehensive neuropsychological battery), and audiometric (pure tone and speech audiometry) functioning. Neuroimaging was also obtained. Results Of 24 individuals with suspected exposure identified by the US Department of State, 21 completed multidisciplinary evaluation an average of 203 days after exposure. Persistent symptoms (>3 months after exposure) were reported by these individuals including cognitive (n = 17, 81%), balance (n = 15, 71%), visual (n = 18, 86%), and auditory (n = 15, 68%) dysfunction, sleep impairment (n = 18, 86%), and headaches (n = 16, 76%). Objective findings included cognitive (n = 16, 76%), vestibular (n = 17, 81%), and oculomotor (n = 15, 71%) abnormalities. Moderate to severe sensorineural hearing loss was identified in 3 individuals. Pharmacologic intervention was required for persistent sleep dysfunction (n = 15, 71%) and headache (n = 12, 57%). Fourteen individuals (67%) were held from work at the time of multidisciplinary evaluation. Of those, 7 began graduated return to work with restrictions in place, home exercise programs, and higher-level work-focused cognitive rehabilitation. Conclusions and Relevance In this preliminary report of a retrospective case series, persistent cognitive, vestibular, and oculomotor dysfunction, as well as sleep impairment and headaches, were observed among US government personnel in Havana, Cuba, associated with reports of directional audible and/or sensory phenomena of unclear origin. These individuals appeared to have sustained injury to widespread brain networks without an associated history of head trauma.

Objective Despite surgical, technological, medical, and anesthetic improvements, patient outcomes following elective neurosurgical procedures can be associated with high morbidity. Enhanced recovery after surgery (ERAS) protocols are multimodal care pathways designed to optimize patient outcomes by addressing pre-, peri-, and post-operative factors. Despite significant data suggesting improved patient outcomes with the adoption of these pathways, development and implementation has been limited in the neurosurgical population. Methods/Results This study protocol was designed to establish the feasibility of a randomized controlled trial to assess the efficacy of implementation of an ERAS protocol on the improvement of clinical and patient reported outcomes and patient satisfaction scores in an elective inpatient spine surgery population. Neurosurgical patients undergoing spinal surgery will be recruited and randomly allocated to one of two treatment arms: ERAS protocol (experimental group) or hospital standard (control group). The experimental group will undergo interventions at the pre-, peri-, and post-operative time points, which are exclusive to this group as compared to the hospital standard group. Conclusions The present proposal aims to provide supporting data for the application of these specific ERAS components in the spine surgery population and provide rationale/justification of this type of care pathway. This study will help inform the design of a future multi-institutional, randomized controlled trial. Results of this study will guide further efforts to limit post-operative morbidity in patients undergoing elective spinal surgery and to highlight the impact of ERAS care pathways in improving patient reported outcomes and satisfaction.

OBJECTIVEPituitary adenomas account for approximately 10% of intracranial tumors and have an estimated prevalence of 15%–20% in the general US population. Resection is the primary treatment for pituitary adenomas, and the transsphenoidal approach remains the most common. The greatest challenge with pituitary adenomas is that 20% of patients develop tumor recurrence. Current approaches to reduce recurrence, such as intraoperative MRI, are costly, associated with high false-positive rates, and not recommended. Pituitary adenomas are known to overexpress folate receptor alpha (FRα), and it was hypothesized that OTL38, a folate analog conjugated to a near-infrared (NIR) fluorescent dye, could provide real-time intraoperative visual contrast of the tumor versus the surrounding nonneoplastic tissues. The preliminary results of this novel clinical trial are presented.METHODSNineteen adult patients who presented with pituitary adenoma were enrolled. Patients were infused with OTL38 2–4 hours prior to surgery. A 4-mm endoscope with both visible and NIR light capabilities was used to visualize the pituitary adenoma and its margins in real time during surgery. The signal-to-background ratio (SBR) was recorded for each tumor and surrounding tissues at various endoscope-to-sella distances. Immunohistochemical analysis was performed to assess the FRα expression levels in all specimens and classify patients as having either high or low FRα expression.RESULTSData from 15 patients (4 with null cell adenomas, 1 clinically silent gonadotroph, 1 totally silent somatotroph, 5 with a corticotroph, 3 with somatotrophs, and 1 somatocorticotroph) were analyzed in this preliminary analysis. Four patients were excluded for technical considerations. Intraoperative NIR imaging delineated the main tumors in all 15 patients with an average SBR of 1.9 ± 0.70. The FRα expression level of the adenomas and endoscope-to-sella distance had statistically significant impacts on the fluorescent SBRs. Additional considerations included adenoma functional status and time from OTL38 injection. SBRs were 3.0 ± 0.29 for tumors with high FRα expression (n = 3) and 1.6 ± 0.43 for tumors with low FRα expression (n = 12; p < 0.05). In 3 patients with immunohistochemistry-confirmed FRα overexpression (2 patients with null cell adenoma and 1 patient with clinically silent gonadotroph), intraoperative NIR imaging demonstrated perfect classification of the tumor margins with 100% sensitivity and 100% specificity. In addition, for these 3 patients, intraoperative residual fluorescence predicted postoperative MRI results with perfect concordance.CONCLUSIONSPituitary adenomas and their margins can be intraoperatively visualized with the preoperative injection of OTL38, a folate analog conjugated to NIR dye. Tumor-to-background contrast is most pronounced in adenomas that overexpress FRα. Intraoperative SBR at the appropriate endoscope-to-sella distance can predict adenoma FRα expression status in real time. This work suggests that for adenomas with high FRα expression, it may be possible to identify margins and to predict postoperative MRI findings.

OBJECTIVEWhen performing ventriculoperitoneal shunt surgery it is necessary to create a subgaleal pocket that is of sufficient size to accommodate a shunt valve. In most cases the valve is placed over the posterior skull where the galea begins to transition to suboccipital neck fascia. Dense fibrous attachments in this region of the skull make it technically awkward to develop the subgaleal valve pocket using standard scissors and a blunt dissection technique. In this report the authors describe a new device that enables surgeons to create the shunt valve pocket by using a simple semi-sharp dissection technique.METHODSThe authors analyzed the deficiencies of the standard valve pocket dissection technique and designed shunt scissors that address the identified shortcomings. These new scissors allow the surgeon to sharply dissect the subgaleal space by using an efficient hand-closing maneuver.RESULTSStandard surgical scissors were modified to create shunt scissors that were tested on the benchtop and used in the operating room. In all cases the shunt scissors proved easy to use and allowed the efficient and reliable creation of a subgaleal valve pocket in a technically pleasing manner.CONCLUSIONSShunt scissors represent an incremental technical advance in the field of neurosurgical shunt operations.

In the setting of recurrent infection and multiple failed reconstruction attempts, the choice of the ideal reconstructive material for salvage cranioplasty remains a source of controversy in the literature. The purpose of this study is to establish the safety and utility of antibiotic-impregnated polymethyl methacrylate (PMMA) for salvage cranioplasty.A prospectively maintained database of all patients who underwent salvage cranioplasty using vancomycin and tobramycin-impregnated methyl methacrylate from January 2011 to July 2013 was reviewed. Vancomycin and tobramycin were mixed in PMMA, which was then applied to a rigidly fixed titanium mesh for reconstruction. Patients' demographics, indications, and outcomes of this technique were evaluated.Nine patients (mean age: 47 years) underwent vancomycin and tobramycin-impregnated PMMA reconstruction with a mean follow-up of 9.3 months (range 3.5-23 months). On average, these patients underwent 4 procedures (range: 1-15), which included repeat craniotomy, debridement for infection, and failed reconstructions over the course of 3.6 years (range: 7 months to 14 years) before salvage cranioplasty. All patients required salvage cranioplasty due to infection, with the most common bacteria isolated in culture being Propionibacterium acnes (n = 3), multiresistant coagulase-negative Staphylococcus (n = 3), methicillin-resistant Staphylococcus aureus (n = 2), and Enterobacter (n = 2). The average size of the craniectomy defect was 130 cm(2), and there were no incidences of postoperative infection, postoperative complications, or need for revisions.To conclude, in short-term follow-up, vancomycin and tobramycin-impregnated PMMA reconstruction appears safe and effective in salvage cranioplasty. Our early report represents a proof of concept--the true test is whether these short-term successes translate to stable long-term results.

e18307 Background: Metastatic spinal cord compression (MSCC) and symptomatic brain metastases (mets) are potential emergencies that demand coordinated multidisciplinary management. Patients (pts) with concerning symptoms are often referred to the Emergency Department (ED) for expedited imaging, but most do not require subsequent ED or inpatient management. Unnecessary ED visits incur substantial cost to the health system and patients, and cause psychosocial stress for patients often near the end-of-life. To improve access to expedited outpatient imaging for high-risk pts and reduce unnecessary ED visits, we developed outpatient rapid MRI protocols and pathways to rule out MSCC and brain mets. Methods: Tailored abbreviated MRI protocols were developed to allow rapid acquisition of brain ( < 13 minutes) and full spine ( < 25 minutes) exams. Dedicated appointments were reserved on the daily MRI schedule. Exams were immediately interpreted and reported by Radiology to the ordering clinician. This pathway was piloted within the Thoracic Oncology group beginning in 10/2018. Results: Referring specialties included Radiation Oncology (50%), Medical Oncology (36%), Pulmonology (7%), and Surgery (7%). For 6 pts who had outpatient rapid brain imaging, median time from order to exam start was 4.3 h (1.8-31) and order to final report 6.8 h (3.2-34.1). Brain mets were found in 4/6 patients. Only 1/4 positive studies required subsequent ED management. For 8 pts referred for rapid spine imaging, median time from order to exam start was 14.4 h (2.2-72.5) and order to final report 16.7 h (4.0-74.4). Only 1 patient was found to have cord compression and required ED/inpatient management. Overall, 86% of patients did not require ED or inpatient admission. 3 pts (all with negative imaging) died a median 13.4 d (1.4-28.3) after order placement. Conclusions: Outpatient rapid MRI protocols facilitate same-day imaging, interpretation, and management, improving care for thoracic oncology pts with new concerning neurologic symptoms and reducing unnecessary ED visits. Future work will expand access beyond Thoracic Oncology and further quantify improvements in cost savings and patient quality of life.

Object As tumors enlarge, they generally grow along paths of least resistance. For pituitary macroadenomas, extrasellar extension into the suprasellar region, cavernous sinus, or sphenoid sinus may occur. The sphenoid sinus is known to have a variable anatomical configuration, and the authors hypothesize that certain anatomical factors may resist tumor expansion into the sphenoid sinus, thereby directing tumor growth into the suprasellar space. In this paper the authors' goal was to determine if sphenoid anatomy influences pituitary tumor growth. Methods The authors conducted a retrospective analysis of 106 consecutive surgical cases of pituitary macroadenoma. Patient demographics, suprasellar extension, sellar width, and features of the sphenoid intersinus septum were recorded on radiographic review. The chi-square test, t-test, logistic regression, and classification and regression tree analysis were used for statistical analysis. Results Of the 106 patients included in the study, 71 (67%) demonstrated suprasellar extension of their tumor. Patients with suprasellar tumor extension had significantly greater intersinus septum width (width > 1.27 mm: OR = 14.32; p = 0.0012) and were significantly older (age > 54 yrs: OR = 3.33; p = 0.0176). They also tended to be male and to have two or more sphenoid partitions (OR = 6.58; p = 0.0306). While patients with suprasellar extension tended to be more likely to have a midline partition and a larger sellar width than their counterparts, these differences did not reach statistical significance. Conclusions Certain aspects of the sphenoid sinus anatomy may function to resist pituitary tumor growth into the sphenoid sinus. Progressive enlargement of pituitary macroadenomas may extend in a suprasellar direction, in part, as a consequence of the sphenoid sinus anatomy.

The International Subarachnoid Aneurysm Trial heralded a paradigm shift in the treatment of intracranial aneurysms. During this same time frame, neurosurgical training programs increased in size and scope. The present study examines the impact of trends in surgical clipping and the endovascular treatment of intracranial aneurysms, over one decade, and the neurosurgical resident complement on the resident teaching environment using the Nationwide Inpatient Sample (NIS).The NIS was used to estimate the number of aneurysms treated with either surgical clipping and endovascular methods from 2002 through 2011 at teaching institutions. Teaching opportunities per year per resident or chief resident were calculated as the ratio of the number of specified cases to the average number of neurosurgical trainees by year. Annualized trends were assessed.Over the study period, the percent change in odds of occurrence of a clipped ruptured aneurysm was -15.6% per year (P0.001) and of ruptured aneurysms undergoing endovascular treatment was 18.7% per year (P 0.001) within teaching institutions. This corresponded to a decline in teaching opportunities for clipped ruptured aneurysms for both residents and chief residents (P 0.001). In contrast, teaching opportunities for endovascular treatment of both ruptured and unruptured aneurysms increased dramatically over the study period.There has been a significant decrease in opportunity for operative exposure to craniotomy for ruptured aneurysm clipping over the past decade, whereas the volume of endovascular procedures for aneurysms has dramatically increased, highlighting the need for a shift in training strategy for those neurosurgeons graduating from residency desiring to subspecialize in neurovascular neurosurgery.

Introduction We sought to identify factors associated with increased length of stay (LOS) and morbidity in patients undergoing resection of pituitary macroadenomas. Methods We reviewed records of 203 consecutive patients who underwent endoscopic endonasal resection of a pituitary macroadenoma (mean age = 55.7 [16-88]) years, volume = 11.3 (1.0-134.3) cm3. Complete resection was possible in 60/29.6% patients. Mean follow-up was 575 days. Multivariate logistic regression was performed using MATLAB. Results Mean LOS was 4.67 (1-66) days and was associated with CSF leak (p = 0.025), lumbar drain placement (p = 0.041; n = 8/3.9% intraoperative, n = 20/9.9% postoperative), and any infection (p = 0.066). Age, diabetes insipidus (n = 17/8.37%), and syndrome of inappropriate antidiuretic hormone secretion (n = 12/5.9%) were not associated with increased LOS (p > 0.2). Postoperative CSF leak in the hospital (n = 21/10.3%) was associated with intraoperative CSF leak (p = 0.002; n = 82/40.4%) and complete resection (p = 0.012). There was no significant association (p > 0.1) between postoperative CSF leak in the hospital following surgery and the use of a fat graft (n = 61/30.1%), nasoseptal flap (155/76.4%), or perioperative lumbar drain placement (n = 8/3.94%). Conclusion Complete resection is associated with increased risk of CSF leak and LOS. Operative strategies including placement of fat graft, nasoseptal flap, or intraoperative lumbar drain placement may have limited value in reducing the risk of postoperative CSF leak.

SummaryObjective The prevalence of clinically silent corticotroph macroadenomas is unknown. Our aim was to determine the prevalence of clinically silent corticotroph macroadenomas among all pituitary macroadenomas. Design Patients scheduled to have transsphenoidal surgery for any sellar mass were prospectively evaluated clinically and biochemically. Patients Adults who were scheduled for transsphenoidal surgery for a sellar mass at a single academic medical centre. Measurements Patients were assessed clinically prior to surgery and graded as having typical, mild or no Cushingoid features. They were assessed biochemically by plasma ACTH and 24-h urine free cortisol (UFC). Excised tissue was examined histologically, and pituitary macroadenomas, examined by immunohistochemistry. Patients with corticotroph macroadenomas were classified as clinically silent if they exhibited no Cushingoid features but had elevated plasma ACTH and/or 24-h UFC. They were classified as totally silent if they exhibited neither Cushingoid features nor elevated plasma ACTH or 24-h UFC. Results Of 124 patients who had pathologically confirmed pituitary macroadenomas, 20 (16%) had corticotroph macroadenomas. Eight (40%) of these were clinically silent, in that they had no Cushingoid features but could be identified biochemically by elevated plasma ACTH (seven) and/or 24-h UFC (three). Five (25%) were totally silent. Conclusions A substantial minority (16%) of pituitary macroadenomas treated surgically are corticotroph adenomas. Of these, 40% are clinically silent but can be recognized by elevated plasma ACTH and/or 24-h UFC. Recognizing these adenomas may influence the surgical approach and provide a marker by which to follow the response to treatment.

Simulated practice may improve resident performance in endoscopic endonasal surgery. Using the NeuroTouch haptic simulation platform, we evaluated resident performance and assessed the effect of simulation training on performance in the operating room. First- (N=3) and second- (N=3) year residents were assessed using six measures of proficiency. Using a visual analog scale, the senior author scored subjects. After the first session, subjects with lower scores were provided with simulation training. A second simulation served as a task-learning control. Residents were evaluated in the operating room over six months by the senior author-who was blinded to the trained/untrained identities-using the same parameters. A nonparametric bootstrap testing method was used for the analysis (Matlab v. 2014a). Simulation training was associated with an increase in performance scores in the operating room averaged over all measures (p=0.0045). This is the first study to evaluate the training utility of an endoscopic endonasal surgical task using a virtual reality haptic simulator. The data suggest that haptic simulation training in endoscopic neurosurgery may contribute to improvements in operative performance. Limitations include a small number of subjects and adjudication bias-although the trained/untrained identity of subjects was blinded. Further study using the proposed methods may better describe the relationship between simulated training and operative performance in endoscopic Neurosurgery.

Object The object of this study was to determine whether aggressive treatment of severe traumatic brain injury (TBI), including invasive intracranial monitoring and decompressive craniectomy, is cost-effective. Methods A decision-analytical model was created to compare costs, outcomes, and cost-effectiveness of 3 strategies for treating a patient with severe TBI. The aggressive-care approach is compared with “routine care,” in which Brain Trauma Foundation guidelines are not followed. A “comfort care” category, in which a single day in the ICU is followed by routine floor care, is included for comparison only. Probabilities of each treatment resulting in various Glasgow Outcome Scale (GOS) scores were obtained from the literature. The GOS scores were converted to quality-adjusted life years (QALYs), based on expected longevity and calculated quality of life associated with each GOS category. Estimated direct (acute and long-term medical care) and indirect (loss of productivity) costs were calculated from the perspective of society. Sensitivity analyses employed a 2D Monte Carlo simulation of 1000 trials, each with 1000 patients. The model was also used to estimate these values for patients 40, 60, and 80 years of age. Results For the average 20-year-old, aggressive care yields 11.7 (± 1.6 [SD]) QALYs, compared with routine care (10.0 ± 1.5 QALYs). This difference is highly significant (p < 0.0001). Although the differences in effectiveness between the 2 strategies diminish with advancing age, aggressive care remains significantly better at all ages. When all costs are considered, aggressive care is also significantly less costly than routine care ($1,264,000 ± $118,000 vs $1,361,000 ± $107,000) for the average 20-year-old. Aggressive care remains significantly less costly until age 80, at which age it costs more than routine care. However, even in the 80-year-old, aggressive care is likely the more cost-effective approach. Comfort care is associated with poorer outcomes at all ages and with higher costs for all groups except 80-year-olds. Conclusions When all the costs of severe TBI are considered, aggressive treatment is a cost-effective option, even for older patients. Comfort care for severe TBI is associated with poor outcomes and high costs, and should be reserved for situations in which aggressive approaches have failed or testing suggests such treatment is futile.

The hypoxia and proliferation index increase with grade in human glial tumors, but there is no agreement whether either has prognostic importance in glioblastomas. We evaluated these end points individually and together in 16 de novo human glioblastomas using antibodies against the 2-nitmimidazole hypoxia detection agent EF5 and the proliferation detection agent Ki-67. Frozen tumor tissue sections were fluorescence-stained for nuclei (Hoechst 33342), hypoxia (anti-EF5 antibodies), and proliferation (anti-Ki-67 antibodies). EF5 binding adjacent to Ki-67+ cells, overall EF5 binding, the ratio of these values, and the proliferation indexwere evaluated. Patients were classified using recursive partitioning analysis and followed up until recurrence and/or death. Recursive partitioning analysis was statistically significant for survival ( P = .0026). Overall EF5 binding, EF5 binding near Ki-67+ cells, and proliferation index did not predict recurrence. Two additional survival analyses based on ratios of the overall EF5 binding to EF5 binding near Ki-67+ cells were performed. High and low ratio values were determined by two cutoff points: ( a ) the 50% value for the ratio [EF5/Ki-67 Binding ]/[Tumor binding ] = Ratio EF5 50% and ( b ) the median EF5 value (75.6%) of the ratio [EF5/Ki-67 Binding ]/[Tumor binding ] = Ratio patients median . On the basis of the Ratio EF5 50% , recurrence ( P = .0074) and survival ( P = .0196) could be predicted. Using the Ratio patients median , only survival could be predicted ( P = .0291). In summary, patients had a worse prognosis if the [EF5/Ki-67 Binding ]/[Tumor binding ] ratio was high. A hypothesis for the mechanisms and translational significance of these findings is discussed.

To determine the impact of cortical Alzheimer disease pathology on shunt responsiveness in individuals treated for idiopathic normal pressure hydrocephalus (iNPH), 37 patients clinically diagnosed with iNPH participated in a prospective study in which performance on neurologic, psychometric, and gait measures before and 4 months after shunting was correlated with amyloid β plaques, neuritic plaques, and neurofibrillary tangles observed in cortical biopsies obtained during shunt insertion. No complications resulted from biopsy acquisition. Moderate to severe pathology was associated with worse baseline cognitive performance and diminished postoperative improvement on NPH symptom severity scales, gait measures, and cognitive instruments compared to patients lacking pathology.

Object The goal of this study was to determine the potential role and current limitations of the da Vinci surgical robot in transoral decompression of craniocervical junction (CCJ). Methods The da Vinci Surgical System was used in 2 cadaver heads with neck and clavicles intact. Both neurosurgeons and otolaryngologists familiar with the open microscopic procedure, as well as the transoral robotic surgical procedure, undertook dissection and decompression of the CCJ. Results The robotic system provided superb illumination and 3D depth perception even several centimeters deep to the posterior oropharyngeal mucosa. The 30° endoscope improved cephalad visualization, eliminating the need to split the soft palate for exposure of the lower clivus. The “intuitive” nature of the da Vinci surgical robot arms provided an advantage in allowing the ability to suture the dura mater in a deep, dark corridor. Because visualization was excellent, tremor-free closure was possible. Conclusions The authors' findings suggest that transoral robotic surgery, with the da Vinci robot system, holds great potential for decompression of the CCJ as well as resection of both extra- and intradural tumors of this region. Further instrument development is necessary and continued investigation is warranted.

Object Recently, the Institute of Medicine examined resident duty hours and their impact on patient safety. Experts have suggested that reducing resident work hours to 56 hours per week would further decrease medical errors. Although some reports have indicated that cutbacks in resident duty hours reduce errors and make resident life safer, few authors have specifically analyzed the effect of the Accreditation Council for Graduate Medical Education (ACGME) duty-hour limits on neurosurgical resident education and the perceived quality of training. The authors have evaluated multiple objective surrogate markers of resident performance and quality of training to determine the impact of the 80-hour workweek. Methods The United States Medical Licensing Examination (USMLE) Step 1 data on neurosurgical applicants entering ACGME-accredited programs between 1998 and 2007 (before and after the implementation of the work-hour rules) were obtained from the Society of Neurological Surgeons. The American Board of Neurological Surgery (ABNS) written examination scores for this group of residents were also acquired. Resident registration for and presentations at the American Association of Neurological Surgeons (AANS) annual meetings between 2002 and 2007 were examined as a measure of resident academic productivity. As a case example, the authors analyzed the distribution of resident training hours in the University of Virginia (UVA) neurosurgical training program before and after the institution of the 80-hour workweek. Finally, program directors and chief residents in ACGME-accredited programs were surveyed regarding the effects of the 80-hour workweek on patient care, resident training, surgical experience, patient safety, and patient access to quality care. Respondents were also queried about their perceptions of a 56-hour workweek. Results Despite stable mean USMLE Step 1 scores for matched applicants to neurosurgery programs between 2000 and 2008, ABNS written examination scores for residents taking the exam for self-assessment decreased from 310 in 2002 to 259 in 2006 (16% decrease, p < 0.05). The mean scores for applicants completing the written examination for credit also did not change significantly during this period. Although there was an increase in the number of resident registrations to the AANS meetings, the number of abstracts presented by residents decreased from 345 in 2002 to 318 in 2007 (7% decrease, p < 0.05). An analysis of the UVA experience suggested that the 80-hour workweek leads to a notable increase in on-call duty hours with a profound decrease in the number of hours spent in conference and the operating room. Survey responses were obtained from 110 program directors (78% response rate) and 122 chief residents (76% response rate). Most chief residents and program directors believed the 80-hour workweek compromised resident training (96%) and decreased resident surgical experience (98%). Respondents also believed that the 80-hour workweek threatened patient safety (96% of program directors and 78% of chief residents) and access to quality care (82% of program directors and 87% of chief residents). When asked about the effects of a 56-hour workweek, all program directors and 98% of the chief residents indicated that resident training and surgical education would be further compromised. Most respondents (95% of program directors and 84% of chief residents) also believed that additional work-hour restrictions would jeopardize patient care. Conclusions Neurological surgery continues to attract top-quality resident applicants. Test scores and levels of participation in national conferences, however, indicate that the 80-hour workweek may adversely affect resident training. Subjectively, neurosurgical program directors and chief residents believe that the 80-hour workweek makes neurosurgical training and the care of patients more difficult. Based on experience with the 80-hour workweek, educators think that a 56-hour workweek would further compromise neurosurgical training and patient care in the US.

Objective: Tremor resulting from damage to midbrain structures is poorly understood and often difficult to treat. The authors report a case of cystic degeneration of the brainstem with resultant Holmes-like tremor which was successfully treated using a stimulating electrode placed in the contralateral ventralis intermedius nucleus (VIM) of the thalamus. Clinical Presentation: A 31-year-old man presented with a multilobulated, multiseptated lesion of the upper brainstem diagnosed after subacute onset of headaches. The patient subsequently developed an incapacitating left-upper-extremity tremor refractory to medical treatment. Intervention: The patient underwent implantation of a deep brain stimulator in the VIM with symptomatic and functional improvement. Conclusions: Deep brain stimulation is an effective and safe intervention for tremor of unusual etiology. Electrode placement should be based on an understanding of the structure-function relationships underlying the various and distinct types of tremor.

Aims: (1) Learn if margins of resection in advanced anterior skull base tumors that are resected via endoscopic-assisted means are comparable with traditional craniofacial resection (CFR). (2) Understand the difference in patient morbidity with endoscopic surgery compared to traditional CFR. Methods: Retrospective review of 41 patients undergoing surgery for comparably staged advanced malignancies of the anterior skull base between 2000 and 2006. Eighteen patients underwent endoscopic surgery and 23 patients underwent traditional CFR for American Joint Committee on Cancer stage III, IV or Kadish stage C lesions of the paranasal sinuses and anterior skull base. Margins were evaluated and follow-up ranged from 3 months to 5 years. Results: Of the 18 patients undergoing endoscopic resections, margins were positive/close in 17% (3/18). Margins were positive/close in 17% (4/23) of patients undergoing CFR. Five complications were seen in 4/18 patients (22%) undergoing endoscopic surgery and 11 postoperative complications were seen in 7/23 patients (30%) undergoing CFR. Mean duration of hospitalization was 5.22 and 7.17 days for the endoscopic and CFR groups, respectively. Conclusions: There does not appear to be increased risk of positive margins in patients with advanced lesions undergoing endoscopic-assisted resection. Furthermore, the incidence of morbidity and duration of stay may be improved with endoscopic techniques.

Obesity is a growing global health problem frequently intractable to current treatment options. Recent evidence suggests that deep brain stimulation (DBS) may be effective and safe in the management of various, refractory neuropsychiatric disorders, including obesity. The authors review the literature implicating various neural regions in the pathophysiology of obesity, as well as the evidence supporting these regions as targets for DBS, in order to explore the therapeutic promise of DBS in obesity. The lateral hypothalamus and ventromedial hypothalamus are the appetite and satiety centers in the brain, respectively. Substantial data support targeting these regions with DBS for the purpose of appetite suppression and weight loss. However, reward sensation associated with highly caloric food has been implicated in overconsumption as well as obesity, and may in part explain the failure rates of conservative management and bariatric surgery. Thus, regions of the brain's reward circuitry, such as the nucleus accumbens, are promising alternatives for DBS in obesity control. The authors conclude that deep brain stimulation should be strongly considered as a promising therapeutic option for patients suffering from refractory obesity.

Object Although neuron transplantation to repair the nervous system has shown promise in animal models, there are few practical sources of viable neurons for clinical application and insufficient approaches to bridge extensive nerve damage in patients. Therefore, the authors sought a clinically relevant source of neurons that could be engineered into transplantable nervous tissue constructs. The authors chose to evaluate human dorsal root ganglion (DRG) neurons due to their robustness in culture. Methods Cervical DRGs were harvested from 16 live patients following elective ganglionectomies, and thoracic DRGs were harvested from 4 organ donor patients. Following harvest, the DRGs were digested in a dispase–collagenase treatment to dissociate neurons for culture. In addition, dissociated human DRG neurons were placed in a specially designed axon expansion chamber that induces continuous mechanical tension on axon fascicles spanning 2 populations of neurons originally plated ∼ 100 μm apart. Results The adult human DRG neurons, positively identified by neuronal markers, survived at least 3 months in culture while maintaining the ability to generate action potentials. Stretch-growth of axon fascicles in the expansion chamber occurred at the rate of 1 mm/day to a length of 1 cm, creating the first engineered living human nervous tissue constructs. Conclusions These data demonstrate the promise of adult human DRG neurons as an alternative transplant material due to their availability, viability, and capacity to be engineered. Also, these data show the feasibility of harvesting DRGs from living patients as a source of neurons for autologous transplant as well as from organ donors to serve as an allograft source of neurons.

Objectives: Previous reports indicate that elevated intracranial pressure (ICP) may cause spontaneous cerebrospinal fluid (CSF) leaks. In this study we examined the clinical diagnosis of benign intracranial hypertension (BIH) in this population using the modified Dandy criteria. Methods: We performed a retrospective review of clinical data and measurements of ICPs after surgical repair. Results: Sixteen patients with spontaneous CSF leaks were surgically treated from 1996 to 2002. In 11 patients with CSF pressure measurements, strict adherence to the modified Dandy criteria definitively confirmed a diagnosis of BIH in 8 patients (72%) and a likely diagnosis in the 3 remaining patients. The mean ICP was 31.1 cm H2O (range, 17.3 to 52 cm H2O), and 81% of the patients were obese middle-aged women. Clinically, all patients had signs and/or symptoms of elevated ICP, such as headache (91%), pulsatile tinnitus (45%), hypertension (45%), balance problems (27%), and visual complaints (18%). Surgical repair was 100% successful in leak cessation over a mean follow-up of 14.1 months. Conclusions: Most patients with spontaneous CSF leaks fulfill the modified Dandy criteria; thus, this disorder appears to be a variant of BIH. Further investigation is needed to determine the exact cause of elevated CSF pressures in this group and whether medical or surgical treatments to correct the intracranial hypertension are warranted.

Traumatic brain injury (TBI) has been associated with intravascular coagulation, which may be a result of thromboplastin released following brain injury. Clots thus formed are lysed by plasmin, which is activated by tissue-type and urokinase-type plasminogen activators (uPA). To evaluate the association between traumatic intravascular coagulation and post-traumatic outcome, uPA knockout (uPA-/-) transgenic mice (n=12) or wild-type littermates (WT; n=12) were anesthetized and subjected to controlled cortical impact (CCI) brain injury. A second group of uPA-/- (n=12) and WT mice (n=12) were subjected to sham injury. Motor function was assessed over 2 weeks using the composite neuroscore test and cognition (learning) was assessed with the Morris Water Maze (MWM) at 2 weeks post-injury, whereupon the animals were sacrificed for cortical lesion volume analysis. Motor function was significantly worse in the brain-injured uPA-/- mice when compared to brain-injured WT mice at 48 h (p

Object. An intracranial pressure (ICP) monitor, from which cerebral perfusion pressure (CPP) is estimated, is recommended in the care of severe traumatic brain injury (TBI). Nevertheless, optimal ICP and CPP management may not always prevent cerebral ischemia, which adversely influences patient outcome. The authors therefore determined whether the addition of a brain tissue oxygen tension (PO2) monitor in the treatment of TBI was associated with an improved patient outcome. Methods. Patients with severe TBI (Glasgow Coma Scale [GCS] score < 8) who had been admitted to a Level I trauma center were evaluated as part of a prospective observational database. Patients treated with ICP and brain tissue PO2 monitoring were compared with historical controls matched for age, pathological features, admission GCS score, and Injury Severity Score who had undergone ICP monitoring alone. Therapy in both patient groups was aimed at maintaining an ICP less than 20 mm Hg and a CPP greater than 60 mm Hg. Among patients whose brain tissue PO2 was monitored, oxygenation was maintained at levels greater than 25 mm Hg. Twenty-five patients with a mean age of 44 ± 14 years were treated using an ICP monitor alone. Twenty-eight patients with a mean age of 38 ± 18 years underwent brain tissue PO2-directed care. The mean daily ICP and CPP levels were similar in each group. The mortality rate in patients treated using conventional ICP and CPP management was 44%. Patients who also underwent brain tissue PO2 monitoring had a significantly reduced mortality rate of 25% (p < 0.05). Conclusions. The use of both ICP and brain tissue PO2 monitors and therapy directed at brain tissue PO2 is associated with reduced patient death following severe TBI.

When a new technology is introduced it is important to empower the bedside practitioner with a resource tool that outlines the purpose, placement procedure, technology application guidelines, and interventions associated with that new technology. This promotes product and patient safety and successful implementation of the new technology. Continued evaluation of bedside clinical practice and the technology used in the care and treatment of the severe brain injured patient can lead to improvements in management and in technology design. Future clinical research initiatives exploring the impact of new technology will enable us to discover cost-effective treatments and interventions that will improve the outcome for a person with traumatic brain injury, a condition that devastates hundreds of thousands of Americans each year.