Establishing a Gold Standard for Noninvasive Identification of Painful Lumbar Discs: Prospective Comparison of Magnetic Resonance Spectroscopy vs Low-Pressure Provocation Discography.

PURPOSE: Verifying lumbar disc pain can present a clinical challenge. Low-pressure provocative discography (PD) has served as the gold standard, although it is invasive and often a challenge to interpret. We reported that magnetic resonance spectroscopy (MRS) biomarkers accurately predict PD results in lumbar discs and improved outcomes for patients with surgery at positive MRS levels versus nonsurgery. To further substantiate MRS for diagnosing painful discs, we report a prospective comparison of 2 MRS-derived measures: NOCISCORE (pain) and SI-SCORE (degeneration severity). METHODS: Lumbar MRS and software-based postprocessing (NOCISCAN-LS, Aclarion Inc.) was performed in 44 discs in 14 patients (prospective cohort [PC]). PC data were compared to prior data used to establish the NOCISCORE (training cohort [TC]). The NOCISCORE was converted to an ordinal value (high/intermediate/low; NOCI+/mild/-) and compared against painful (P) versus nonpainful (NP) control diagnosis (PD) for 19 discs where PD was performed in the PC (12 NP; 7 P). Sensitivity, specificity, and positive and negative predictive values were calculated. The SI-SCORE was compared against MRI Pfirrmann Grades for 465 discs in 126 patients (PC plus TC). RESULTS: For the PC, MRS (NOCI+/-) compared to PD (P/NP) with an accuracy of 87% and sensitivity and specificity of 100%. The positive and negative predictive values of MRS were 100%. NOCISCOREs were significantly higher for PD+ versus PD- discs for PC and TC (P < 0.05), and the NOCISCORE distributions for PD+/- group were not statistically different between the PC and TC (P > 0.05). SI-SCORES differed between Pfirrmann Grades 1 and 2 (less degenerated) versus Grades 3 and 4 (more degenerated; P < 0.05), with a progressively decreasing trend with Pfirrmann Grades 1-5. CONCLUSION: These current data provide prospective confirmation of the predictive value of disc MRS for distinguishing painful discs and for assessing the disc structural integrity. CLINICAL RELEVANCE: NOCISCAN is an adoptable, noninvasive, and objectively quantitative test to improve management of low back pain patients.

Examining barriers to implementing a surgical-site infection bundle.

BACKGROUND: Surgical-site infections (SSIs) can be catastrophic. Bundles of evidence-based practices can reduce SSIs but can be difficult to implement and sustain. OBJECTIVE: We sought to understand the implementation of SSI prevention bundles in 6 US hospitals. DESIGN: Qualitative study. METHODS: We conducted in-depth semistructured interviews with personnel involved in bundle implementation and conducted a thematic analysis of the transcripts. SETTING: The study was conducted in 6 US hospitals: 2 academic tertiary-care hospitals, 3 academic-affiliated community hospitals, 1 unaffiliated community hospital. PARTICIPANTS: In total, 30 hospital personnel participated. Participants included surgeons, laboratory directors, clinical personnel, and infection preventionists. RESULTS: Bundle complexity impeded implementation. Other barriers varied across services, even within the same hospital. Multiple strategies were needed, and successful strategies in one service did not always apply in other areas. However, early and sustained interprofessional collaboration facilitated implementation. CONCLUSIONS: The evidence-based SSI bundle is complicated and can be difficult to implement. One implementation process probably will not work for all settings. Multiple strategies were needed to overcome contextual and implementation barriers that varied by setting and implementation climate. Appropriate adaptations for specific settings and populations may improve bundle adoption, fidelity, acceptability, and sustainability.

Patients' experiences and compliance with preoperative screening and decolonization.

BACKGROUND: To improve adherence with pre-surgical screening for Staphylococcus aureus nasal carriage and decolonization, we need more information about patients' experiences with these protocols. METHODS: We surveyed patients undergoing orthopedic, neurosurgical, or cardiac operations at Johns Hopkins Hospitals (JHH), the University of Iowa Hospitals and Clinics (UIHC) at MercyOne Northeast Iowa Neurosurgery (MONIN) to assess patients' experiences with decolonization protocols. RESULTS: Five hundred thirty-four patients responded. Respondents at JHH were significantly more likely than those at the UIHC to report using mupirocin and were significantly more likely than those at the UIHC and MONIN to feel they received adequate information about surgical site infection (SSI) prevention and decolonization. Respondents at JHH were the least likely to not worry about SSI and they were more willing to do anything they could to prevent SSI. Few patients reported barriers to adherence and side effects of mupirocin or chlorhexidine. CONCLUSION: Respondents did not report either major side effects or barriers to adherence. Patients varied in their level of concern about SSI, their willingness to invest effort in preventing SSI, and their assessments of preoperative information. To improve patients' adherence, clinicians and hospitals should assess their patients' needs and desires and tailor their preoperative processes, education, and prophylaxis accordingly.

Intra-operative emergence of occult dural arteriovenous fistula after middle meningeal artery embolization for chronic subdural hematoma: Case report and literature review.

Dural arteriovenous fistulae of the middle meningeal artery (MMA-dAVF) are high risk lesions that can lead to intracranial hemorrhage. We describe the case of an adult male that presented with chronic subdural hematomas and was treated with burr hole craniotomy plus middle meningeal artery (MMA) embolization. Although the pre-embolization angiogram showed no signs of a fistula, a fistula arising from the MMA and draining into the superior sagittal sinus emerged intra-operatively. To our knowledge, this is the first case of intra-operative emergence of occult MMA-dAVF with intracranial drainage during MMA embolization for chronic subdural hematoma treatment. This observation supports monitoring for and embolizing spontaneous MMA-dAVF following MMA embolization.

Association between interhospital transfer and increased in-hospital mortality in patients with spinal epidural abscesses.

BACKGROUND CONTEXT: Spinal epidural abscess (SEA) is an uncommon yet serious infection, associated with significant morbidity and mortality. Patients diagnosed with SEA often require surgical interventions or critical care services that are not available at community hospitals and are therefore transferred to tertiary care centers. Little is known about the effects of interhospital transfer on acute outcomes for patients with SEA. PURPOSE: To study the effects of interhospital transfer on acute outcomes for patients with SEA. STUDY DESIGN: Cross sectional analysis using the 2009 to 2017 National Inpatient Sample (NIS). PATIENT SAMPLE: Using the 2009 to 2017 NIS, we identified cases of SEA using ICD, Ninth, or Tenth Revision diagnosis codes 324.1 & G06.1. OUTCOME MEASURES: Our primary endpoint was in hospital mortality. METHODS: The association between interhospital transfer and inpatient mortality was assessed using multivariable logistic regression to adjust for potential covariates. Patient and hospital factors associated with interhospital transfer were assessed in a secondary analysis. RESULTS: A total of 21.5% of patient with SEA were treated after transfer from another hospital. After adjusting for covariates, those who presented after transfer had higher odds of death during hospitalization (OR: 1.51, 95% CI 1.27-1.78, p<.001). Transferred patients were significantly more likely to live in rural communities (11.4 % vs. 5.3 % for nontransferred patients). CONCLUSIONS: Interhospital transfer, which occurred more frequently in patients from rural hospitals, was associated with death even after controlling for disease severity. Addressing healthcare delivery disparities across the US, including across the rural-urban spectrum, will require better understanding of the observed increased mortality of interhospital transfer as a preventable source of in-hospital mortality for SEA.

Racial Disparities in Outcomes After Spine Surgery: A Systematic Review and Meta-Analysis.

OBJECTIVE: Racial disparities are a major issue in health care but the overall extent of the issue in spinal surgery outcomes is unclear. We conducted a systematic review/meta-analysis of disparities in outcomes among patients belonging to different racial groups who had undergone surgery for degenerative spine disease. METHODS: We searched Ovid MEDLINE, Scopus, Cochrane Review Database, and ClinicalTrials.gov from inception to January 20, 2021 for relevant articles assessing outcomes after spine surgery stratified by race. We included studies that compared outcomes after spine surgery for degenerative disease among different racial groups. RESULTS: We found 30 studies that met our inclusion criteria (28 articles and 2 published abstracts). We included data from 20 cohort studies in our meta-analysis (3,501,830 patients), which were assessed to have a high risk of observation/selection bias. Black patients had a 55% higher risk of dying after spine surgery compared with white patients (relative risk [RR], 1.55, 95% confidence interval [CI], 1.28-1.87; I2 = 70%). Similarly, black patients had a longer length of stay (mean difference, 0.93 days; 95% CI, 0.75-1.10; I2 = 73%), and higher risk of nonhome discharge (RR, 1.63; 95% CI, 1.47-1.81; I2 = 89%), and 30-day readmission (RR, 1.45; 95% CI, 1.03-2.04; I2 = 96%). No significant difference was noted in the pooled analyses for complication or reoperation rates. CONCLUSIONS: Black patients have a significantly higher risk of unfavorable outcomes after spine surgery compared with white patients. Further work in understanding the reasons for these disparities will help develop strategies to narrow the gap among the racial groups.

Improving the Usability of 5-Aminolevulinic Acid Fluorescence-Guided Surgery by Adding an Optimized Secondary Light Source.

BACKGROUND: Tumors that take up and metabolize 5-aminolevulinic acid emit bright pink fluorescence when illuminated with blue light, aiding surgeons in identifying the margin of resection. The adoption of this method is hindered by the blue light illumination, which is too dim to safely operate under and therefore necessitates switching back and forth from white-light mode. The aim of this study was to examine the addition of an optimized secondary illuminant adapter to improve usability of blue-light mode without degrading tumor contrast. METHODS: Color science methods were used to evaluate the color of the secondary illuminant and its impact on color rendering index as well as the tumor-to-background color contrast in data collected from 7 patients with high-grade gliomas (World Health Organization grade III and IV). A secondary illuminant adapter was built to provide 475-600 nm light the intensity of which can be controlled by the surgeon and was evaluated in 2 additional patients. RESULTS: Secondary illuminant color had opposing effects on color rendering index and tumor-to-background color contrast; providing surgeon control of intensity allows this trade-off to be balanced in real time. Demonstration in 2 high-grade glioma cases confirms this, showing that additional visibility adds value when intensity can be controlled by the surgeon. CONCLUSIONS: Addition of a secondary illuminant may mitigate surgeon complaints that the operative field is too dark under the blue light illumination required for 5-aminolevulinic acid fluorescence guidance by providing improved color rendering index without completely sacrificing tumor-to-background color contrast.

Congress of neurological surgeons systematic review and evidence-based clinical practice parameter guidelines for the treatment of adults with newly diagnosed glioblastoma: Introduction and Methods.

PURPOSE: This is an update of the evidence-based guideline for management of newly diagnosed glioblastomas sponsored by the American Association of Neurological Surgeons (AANS) and Congress of Neurological Surgeons (CNS) initially published in 2008. The objective is to update evidence-based management of newly diagnosed glioblastomas over all commonly used diagnostic and treatment modalities in regularly encountered clinical situations. METHODS: A multidisciplinary writing group was assembled to create documents related to imaging, cytoreductive surgery, neuropathology, radiation therapy, chemotherapy and emerging developments. Questions from the prior set of guidelines, and new and modified questions were used to guide a search of the scientific literature since the last guideline search was completed in June 2005. Citations were screened, classified and used as evidence to create recommendations addressing the questions in a manner that was directly linked to this evidence. RESULTS: The sixteen writers produced 34 questions resulting in eight Level I recommendations, eleven Level II recommendations, and 27 Level II recommendations across all the topics. In some instances, insufficient data was available to answer all or part of a question and this is stated and explained. CONCLUSIONS: This series of guidelines is based upon relevant evidence in the literature related to the management of newly diagnosed glioblastomas. They set a benchmark for the management of this disease while highlighting key areas of weakness in our knowledge and suggest directions for future basic and clinical research to improve evidence quality and recommendation strength.

Cytoreductive surgery in the management of newly diagnosed glioblastoma in adults: a systematic review and evidence-based clinical practice guideline update.

TARGET POPULATION: These recommendations apply to adults with newly diagnosed or suspected glioblastoma. QUESTION: What is the effect of extent of surgical resection on patient outcome in the initial management of adult patients with suspected newly diagnosed glioblastoma? RECOMMENDATION: Level II: Maximal cytoreductive surgery is recommended in adult patients with suspected newly diagnosed supratentorial glioblastoma with gross total resection defined as removal of contrast enhancing tumor. Level III: Biopsy, subtotal resection, or gross total resection is suggested depending on medical comorbidities, functional status, and location of tumor if maximal resection may cause significant neurologic deficit. QUESTION: What is the role of cytoreductive surgery in adults with newly diagnosed bi-frontal "butterfly" glioblastoma? RECOMMENDATION: Level III: Resection of newly diagnosed bi-frontal "butterfly" glioblastoma is suggested to improve overall survival over biopsy alone. QUESTION: What is the goal of cytoreductive surgery in elderly adult patients with newly diagnosed glioblastoma? RECOMMENDATION: Level III: Elderly patients (> 65 years) show survival benefit with gross total resection and it is suggested they undergo cytoreductive surgery. QUESTION: What is the role of advanced intraoperative guidance techniques in cytoreductive surgery in adults with newly diagnosed glioblastoma? RECOMMENDATION: Level III: The use of intraoperative guidance adjuncts such as intraoperative MRI (iMRI) or 5-aminolevulinic acid (5-ALA) are suggested to maximize extent of resection in newly diagnosed glioblastoma. There is insufficient evidence to make a suggestion on the use of fluorescein, indocyanine green, or intraoperative ultrasound.

The role of neuropathology in the management of newly diagnosed glioblastoma: a systematic review and evidence-based clinical practice guideline.

TARGET POPULATION: These recommendations apply to adult patients with newly diagnosed or suspected glioblastoma (GBM) QUESTION : For adult patients with newly diagnosed GBM does testing for Isocitrate Dehydrogenase 1 or 2 (IDH 1/2) mutations afford benefit beyond standard histopathology in providing accurate classification and outcome prognostication? Level III IDH 1/2 mutational status by immunohistochemistry (IHC) and/or sequencing is suggested for classification and prognostic information. Level III Non-canonical IDH 1/2 mutations are very rare in patients aged 55 or older and universal testing of variant mutations by sequence analysis is not suggested for this age range. QUESTION: For adult patients with lower grade infiltrating astrocytomas (WHO grades II and III) can the IDH-wildtype status designation supersede histopathology to predict prognosis and biologic relevance to eventual behavior as a GBM? Level III The designation of infiltrating astrocytomas (WHO grades II and III) as IDH-wildtype is not suggested as sufficient for a higher grade designation alone. Level III It is suggested that IDH-wildtype WHO grades II and III astrocytomas be tested for molecular-genetic alterations typical of IDH-wildtype GBM such as EGFR amplification, gain of chromosome 7/loss of chromosome 10 and TERT-p mutation to substantiate prediction of behavior similar to IDH-wildtype glioblastoma. Level III It is suggested that a diagnosis of diffuse astrocytic glioma, IDH-wildtype, with molecular features of GBM, WHO grade IV be rendered for infiltrating astrocytomas that lack histologic criteria of GBM but harbors molecular-genetic alterations of IDH-wildtype glioblastoma. QUESTION: For adult patients with newly diagnosed infiltrating glioma arising in the midline does testing for H3-K27M mutations provide information beyond that gained by histopathology for accurate classification and outcome prognostication? Level III It is suggested that infiltrating gliomas arising in midline anatomic locations be tested for the H3-K27M mutation as they tend to exhibit WHO grade IV behavior even if they lack histologic criteria for glioblastoma.

The role of imaging for the management of newly diagnosed glioblastoma in adults: a systematic review and evidence-based clinical practice guideline update.

TARGET POPULATION: These recommendations apply to adults with a newly diagnosed lesion with a suspected or histopathologically proven glioblastoma (GBM). QUESTION: What are the optimal imaging techniques to be used in the management of a suspected glioblastoma (GBM), specifically: which imaging sequences are critical for most accurately identifying or diagnosing a GBM and distinguishing this tumor from other tumor types? RECOMMENDATIONS: Critical Imaging for the Identification and Diagnosis of Glioblastoma Level II: In patients with a suspected GBM, it is recommended that the minimum magnetic resonance imaging (MRI) exam should be an anatomic exam with both T2 weighted, FLAIR and pre- and post-gadolinium contrast enhanced T1 weighted imaging. The addition of diffusion and perfusion weighted MR imaging can assist in the assessment of suspected GBM for the purposes of distinguishing GBM from other tumor types. Computed tomography (CT) can provide additional information regarding calcification or hemorrhage and also can be useful for subjects who are unable to undergo MR imaging. At a minimum, these anatomic sequences can help identify a lesion as well as its location, and potential for surgical intervention. Improvement of diagnostic specificity with the addition of non-anatomic (physiologic imaging) to anatomic imaging Level II: One blinded prospective study and a significant number of case series support the addition of diffusion and perfusion weighted MR imaging in the assessment of suspected GBM, for the purposes of distinguishing GBM from other tumor types (e.g., primary CNS lymphoma or metastases). Level III: It is suggested that magnetic resonance spectroscopy (MRS) and nuclear medicine imaging (PET 18F-FDG and 11C-MET) be used to provide additional support for the diagnosis of GBM.

The role of radiation therapy in treatment of adults with newly diagnosed glioblastoma multiforme: a systematic review and evidence-based clinical practice guideline update.

TARGET POPULATION: These recommendations apply to adult patients diagnosed with newly diagnosed glioblastoma. QUESTION 1 : In adult patients (aged 65 and under) with newly diagnosed glioblastoma, is the addition of radiation therapy (RT) more beneficial than management without RT in improving survival? RECOMMENDATIONS: Level I: Radiation therapy (RT) is recommended for the treatment of newly diagnosed malignant glioblastoma in adults. QUESTION 2 : In adult patients (aged 65 and under) with newly diagnosed glioblastoma, is the RT regimen of 60 Gy given in 2 Gy daily fractions more beneficial than alternative regimens in providing survival benefit while minimizing toxicity? RECOMMENDATIONS: Level I: Treatment schemes should include dosage of up to 60 Gy given in 2 Gy daily fractions that includes the enhancing area. QUESTION 3 : In adult patients (aged 65 and under) with newly diagnosed glioblastoma, is a tailored target volume superior to regional RT for reduction of radiation-induced toxicity while maintaining efficacy? RECOMMENDATION: Level II: It is recommended that radiation therapy planning include 1-2 cm margin around the radiographically T1 weighted contrast-enhancing tumor volume or the T2 weighted abnormality on MRI. Level III: Recalculation of the radiation volume during RT treatment may be necessary to reduce the radiated volume of normal brain since the volume of surgical defect will change during the long period of RT. QUESTION 4 : In adult patients (aged 65 and under) with newly diagnosed glioblastoma, does the addition of RT of the subventricular zone to standard tumor volume treatment improve tumor control and overall survival? RECOMMENDATION: No recommendation can be formulated as there is contradictory evidence in favor of and against intentional radiation of the subventricular zone (SVZ) QUESTION 5 : In elderly (age > 65 years) and/or frail patients with newly diagnosed glioblastoma, does the addition of RT to surgical intervention improve disease control and overall survival? RECOMMENDATION: Level I: Radiation therapy is recommended for treatment of elderly and frail patients with newly diagnosed glioblastoma to improve overall survival. QUESTION 6 : In elderly (age > 65 years) and/or frail patients with newly diagnosed glioblastoma, does modification of RT dose and fractionation scheme from standard regimens decrease toxicity and improve disease control and survival? RECOMMENDATION: Level II: Short RT treatment schemes are recommended in frail and elderly patients as compared to conventional 60 Gy given in 2 daily fractions because overall survival is not different while RT risk profile is better for the short RT scheme. Level II: The 40.05 Gy dose given in 15 fractions or 25 Gy dose given in 5 fractions or 34 Gy dose given in 10 fractions should be considered as appropriate doses for Short RT treatments in elderly and/or frail patients. QUESTION 7 : In adult patients with newly diagnosed glioblastoma is there advantage to delaying the initiation of RT instead of starting it 2 weeks after surgical intervention in decreasing radiation-induced toxicity and improving disease control and survival? RECOMMENDATION: Level III: It is suggested that RT for patients with newly diagnosed GBM starts within 6 weeks of surgical intervention as compared to later times. There is insufficient evidence to recommend the optimal specific post-operative day within the 6 weeks interval to start RT for adult patients with newly diagnosed glioblastoma that have undergone surgical resection. QUESTION 8 : In adult patients with newly diagnosed supratentorial glioblastoma is Image-Modulated RT (IMRT) or similar techniques as effective as standard regional RT in providing tumor control and improve survival? RECOMMENDATION: Level III: There is no evidence that IMRT is a better RT delivering modality when compared to conventional RT in improving overall survival in adult patients with newly diagnosed glioblastoma. Hence, IMRT should not be preferred over the Conventional RT delivery modality. QUESTION 9 : In adult patients with newly diagnosed glioblastoma does the use of radiosensitizers with RT improve the efficacy of RT as determined by disease control and overall survival? RECOMMENDATION: Level III: Iododeoxyuridine is not recommended to be used as radiosensitizer during RT treatment for patients with newly diagnosed GBM QUESTION 10 : In adult patients with newly diagnosed glioblastoma is the use of Ultrafractionated RT superior to standard fractionation regimens in improving disease control and survival? RECOMMENDATION: There is insufficient evidence to formulate a recommendation regarding the use of ultrafractionated RT schemes and patient population that could benefit from it. QUESTION 11 : In patients with poor prognosis with newly diagnosed glioblastoma is hypofractionated RT indicated instead of a standard fractionation regimen as measured by extent of toxicity, disease control and survival? RECOMMENDATION: Level I: Hypofractionated RT schemes may be used for patients with poor prognosis and limited survival without compromising response. There is insufficient evidence in the literature for us to be able to recommend the optimal hypofractionated RT scheme that will confer longest overall survival and/or confer the same overall survival with less toxicities and shorter treatment time. QUESTION 12 : In adult patients with newly diagnosed glioblastoma is the addition of brachytherapy to standard fractionated RT indicated to improve disease control and survival? RECOMMENDATION: Level I: Brachytherapy as a boost to external beam RT has not been shown to be beneficial and is not recommended in the routine management of patients with newly diagnosed GBM. QUESTION 13 : In elderly patients (> 65 year old) with newly diagnosed glioblastoma under what circumstances is accelerated hyperfractionated RT indicated instead of a standard fractionation regimen as measured by extent of toxicity, disease control and survival? RECOMMENDATION: Level III: Accelerated Hyperfractionated RT with a total RT dose of 45 Gy or 48 Gy has been shown to shorten the treatment time without detriment in survival when compared to conventional external beam RT and should be considered as an option for treatment of elderly patients with newly diagnosed GBM. QUESTION 14 : In adult patients with newly diagnosed glioblastoma is the addition of Stereotactic Radiosurgery (SRS) boost to conventional standard fractionated RT indicated to improve disease control and survival? RECOMMENDATION: Level I: Stereotactic Radiosurgery boost to external beam RT has not been shown to be beneficial and is not recommended in patients undergoing routine management of newly diagnosed malignant glioma.

Study Design in Neurosurgical Research: Considerations for Observational and Experimental Cohort Studies.

There is inadequate neurosurgical literature discussing appropriate clinical study design. Here, we explore considerations for 2 fundamental study designs of epidemiology: experimental and observational cohort studies, through examples of theoretical yet realistic neurosurgical research questions. By examining 2 common neurosurgical procedures-namely, subdural drains for evacuation of chronic subdural hematoma, and the utility of navigation for placing external ventricular drains-we characterize the framework of cohort study models for clinical research applications.

Determining an Appropriate Outcome Measure in Neurosurgical Research: Investigating Meaningful, Valid, and Practical Metrics.

Given the rapidly evolving pace of research and technology in the neurosurgical field, it is critical to consider the parameters of valid, practical, and meaningful study outcome measures. Here we review fundamental aspects of selecting outcome measures in the context of neurosurgical research. Exemplifying work in meningiomas and high-grade gliomas, we delineate a proposed framework for identifying an appropriate outcome measure. Four fundamental components of an outcome measure are defined and characterized: understanding characteristics of a good outcome measure; developing a research question to address an outcome measure; defining the outcome measure, and considering limitations of an outcome measure. This four-part framework enhances and promotes the methodology for determining if an outcome measure is valid, practical, and ultimately meaningful.

Congress of Neurological Surgeons Systematic Review and Evidence-Based Guidelines on the Role of Steroids in the Treatment of Adults With Metastatic Brain Tumors.

QUESTION: Do steroids improve neurological symptoms and/or quality of life in patients with metastatic brain tumors compared to supportive care only or other treatment options? If steroids are given, what dose should be used? TARGET POPULATION: These recommendations apply to adults diagnosed with brain metastases. RECOMMENDATIONS: STEROID THERAPY VERSUS NO STEROID THERAPYAsymptomatic brain metastases patients without mass effectInsufficient evidence exists to make a treatment recommendation for this clinical scenario.Brain metastases patients with mild symptoms related to mass effect Level 3: Corticosteroids are recommended to provide temporary symptomatic relief of symptoms related to increased intracranial pressure and edema secondary to brain metastases. It is recommended for patients who are symptomatic from metastatic disease to the brain that a starting dose of 4 to 8 mg/d of dexamethasone be considered.Brain metastases patients with moderate to severe symptoms related to mass effect Level 3: Corticosteroids are recommended to provide temporary symptomatic relief of symptoms related to increased intracranial pressure and edema secondary to brain metastases. If patients exhibit severe symptoms consistent with increased intracranial pressure, it is recommended that higher doses such as 16 mg/d or more be considered. CHOICE OF STEROID: Level 3: If corticosteroids are given, dexamethasone is the best drug choice given the available evidence.Duration of Corticosteroid Administration Level 3: Corticosteroids, if given, should be tapered as rapidly as possible but no faster than clinically tolerated, based upon an individualized treatment regimen and a full understanding of the long-term sequelae of corticosteroid therapy.Given the very limited number of studies (2) which met the eligibility criteria for the systematic review, these are the only recommendations that can be offered based on this methodology.The full guideline can be found at https://www.cns.org/guidelines/guidelines-treatment-adults-metastatic-brain-tumors/chapter_7.

Congress of Neurological Surgeons Systematic Review and Evidence-Based Guidelines for the Treatment of Adults With Metastatic Brain Tumors: Executive Summary.

BACKGROUND: The Congress of Neurological Surgeons systematic review and evidence-based clinical practice parameter guidelines for the treatment of adults with metastatic brain tumors was first published in 2010. Because of the time elapsed since that publication, an update of this set of guidelines based on literature published since is now indicated. OBJECTIVE: To establish the best evidence-based management of metastatic brain tumors over all commonly used diagnostic and treatment modalities in regularly encountered clinical situations. METHODS: Literature searches regarding management of metastatic brain tumors with whole brain radiation therapy, surgery, stereotactic radiosurgery, chemotherapy, prophylactic anticonvulsants, steroids, instances of multiple brain metastases, and emerging and investigational therapies were carried out to answer questions designed by consensus of a multidisciplinary writing group. RESULTS: Recommendations were created and their strength linked to the quality of the literature data available thus creating an evidence-based guideline. Importantly, shortcomings and biases to the literature data are brought out so as to provide guidance for future investigation and improvements in the management of patients with metastatic brain tumors. CONCLUSION: This series of guidelines was constructed to assess the most current and clinically relevant evidence for management of metastatic brain tumors. They set a benchmark regarding the current evidence base for this management while also highlighting important key areas for future basic and clinical research, particularly on those topics for which no recommendations could be formulated.The full guideline can be found at: https://www.cns.org/guidelines-treatment-adults-metastatic-brain-tumors/chapter_1.

Congress of Neurological Surgeons Systematic Review and Evidence-Based Guidelines on the Role of Chemotherapy in the Management of Adults With Newly Diagnosed Metastatic Brain Tumors.

QUESTION 1: Should patients with brain metastases receive chemotherapy in addition to whole brain radiotherapy (WBRT) for the treatment of their brain metastases? TARGET POPULATION: This recommendation applies to adult patients with newly diagnosed brain metastases amenable to both chemotherapy and radiation treatment. RECOMMENDATIONS: Level 1: Routine use of chemotherapy following WBRT for brain metastases is not recommended. Level 3: Routine use of WBRT plus temozolomide is recommended as a treatment for patients with triple negative breast cancer. QUESTION 2: Should patients with brain metastases receive chemotherapy in addition to stereotactic radiosurgery (SRS) for the treatment of their brain metastases? RECOMMENDATIONS: Level 1: Routine use of chemotherapy following SRS is not recommended. Level 2: SRS is recommended in combination with chemotherapy to improve overall survival and progression free survival in lung adenocarcinoma patients. QUESTION 3: Should patients with brain metastases receive chemotherapy alone? RECOMMENDATION: Level 1: Routine use of cytotoxic chemotherapy alone for brain metastases is not recommended as it has not been shown to increase overall survival.Please see the full-text version of this guideline (https://www.cns.org/guidelines/guidelines-treatment-adults-metastatic-brain-tumors/chapter_5) for the target population of each recommendation.

Congress of Neurological Surgeons Systematic Review and Evidence-Based Guidelines on the Role of Surgery in the Management of Adults With Metastatic Brain Tumors.

Please see the full-text version of this guideline https://www.cns.org/guidelines/guidelines-treatment-adults-metastatic-brain-tumors/chapter_2) for the target population of each recommendation listed below. SURGERY FOR METASTATIC BRAIN TUMORS AT NEW DIAGNOSIS QUESTION: Should patients with newly diagnosed metastatic brain tumors undergo surgery, stereotactic radiosurgery (SRS), or whole brain radiotherapy (WBRT)? RECOMMENDATIONS: Level 1: Surgery + WBRT is recommended as first-line treatment in patients with single brain metastases with favorable performance status and limited extracranial disease to extend overall survival, median survival, and local control. Level 3: Surgery plus SRS is recommended to provide survival benefit in patients with metastatic brain tumors Level 3: Multimodal treatments including either surgery + WBRT + SRS boost or surgery + WBRT are recommended as alternatives to WBRT + SRS in terms of providing overall survival and local control benefits. SURGERY AND RADIATION FOR METASTATIC BRAIN TUMORS QUESTION: Should patients with newly diagnosed metastatic brain tumors undergo surgical resection followed by WBRT, SRS, or another combination of these modalities? RECOMMENDATIONS: Level 1: Surgery + WBRT is recommended as superior treatment to WBRT alone in patients with single brain metastases. Level 3: Surgery + SRS is recommended as an alternative to treatment with SRS alone to benefit overall survival. Level 3: It is recommended that SRS alone be considered equivalent to surgery + WBRT. SURGERY FOR RECURRENT METASTATIC BRAIN TUMORS QUESTION: Should patients with recurrent metastatic brain tumors undergo surgical resection? RECOMMENDATIONS: Level 3: Craniotomy is recommended as a treatment for intracranial recurrence after initial surgery or SRS. SURGICAL TECHNIQUE AND RECURRENCE QUESTION A: Does the surgical technique (en bloc resection or piecemeal resection) affect recurrence? RECOMMENDATION: Level 3: En bloc tumor resection, as opposed to piecemeal resection, is recommended to decrease the risk of postoperative leptomeningeal disease when resecting single brain metastases. QUESTION B: Does the extent of surgical resection (gross total resection or subtotal resection) affect recurrence? RECOMMENDATION: Level 3: Gross total resection is recommended over subtotal resection in recursive partitioning analysis class I patients to improve overall survival and prolong time to recurrence. The full guideline can be found at https://www.cns.org/guidelines/guidelines-treatment-adults-metastatic-brain-tumors/chapter_2.

CD271+ Cells Are Diagnostic and Prognostic and Exhibit Elevated MAPK Activity in SHH Medulloblastoma.

The extensive heterogeneity both between and within the medulloblastoma subgroups underscores a critical need for variant-specific biomarkers and therapeutic strategies. We previously identified a role for the CD271/p75 neurotrophin receptor (p75NTR) in regulating stem/progenitor cells in the SHH medulloblastoma subgroup. Here, we demonstrate the utility of CD271 as a novel diagnostic and prognostic marker for SHH medulloblastoma using IHC analysis and transcriptome data across 763 primary tumors. RNA sequencing of CD271+ and CD271- cells revealed molecularly distinct, coexisting cellular subsets, both in vitro and in vivo MAPK/ERK signaling was upregulated in the CD271+ population, and inhibiting this pathway reduced endogenous CD271 levels, stem/progenitor cell proliferation, and cell survival as well as cell migration in vitro Treatment with the MEK inhibitor selumetinib extended survival and reduced CD271 levels in vivo, whereas, treatment with vismodegib, a well-known smoothened (SMO) inhibitor currently in clinical trials for the treatment of recurrent SHH medulloblastoma, had no significant effect in our models. Our study demonstrates the clinical utility of CD271 as both a diagnostic and prognostic tool for SHH medulloblastoma tumors and reveals a novel role for MEK inhibitors in targeting CD271+ SHH medulloblastoma cells.Significance: This study identifies CD271 as a specific and novel biomarker of SHH-type medulloblastoma and that targeting CD271+ cells through MEK inhibition represents a novel therapeutic strategy for the treatment of SHH medulloblastoma. Cancer Res; 78(16); 4745-59. ©2018 AACR.

Congress of Neurological Surgeons Systematic Review and Evidence-Based Guidelines on the Treatment of Adults With Vestibular Schwannomas: Executive Summary.

BACKGROUND: Vestibular schwannomas (VS) are uncommon lesions that are a substantial challenge to the neurosurgeons, otologists, and radiation oncologists who undertake their clinical management. A starting point to improving the current knowledge is to define the benchmarks of the current research studying VS management using evidence-based techniques in order to allow meaningful points of departure for future scientific and clinical research. OBJECTIVE: To establish the best evidence-based management of VS, including initial otologic evaluation, imaging diagnosis, use of surgical techniques, assessment of tumor pathology, and the administration of radiation therapy. METHODS: Multidisciplinary writing groups were identified to design questions, literature searches, and collection and classification of relevant findings. This information was then translated to recommendations based on the strength of the available literature. RESULTS: This guideline series yielded some level 2 recommendations and a greater number of level 3 recommendations directed at the management of VS. Importantly, in some cases, a number of well-designed questions and subsequent searches did not yield information that allowed creation of a meaningful and justifiable recommendation. CONCLUSION: This series of guidelines was constructed to assess the most current and clinically relevant evidence for the management of VS. They set a benchmark regarding the current evidence base for this type of tumor while also highlighting important key areas for future basic and clinical research, particularly on those topics for which no recommendations could be formulated. The full guidelines can be found at: https://www.cns.org/guidelines/guidelines-management-patients-vestibular-schwannoma.