Extreme-aged patients (≥ 85 years) experience similar outcomes as younger geriatric patients following chronic subdural hematoma evacuation: a matched cohort study.

Subdural hematoma (SDH) evacuation represents one of the most frequently performed neurosurgical procedures. Several reports cite a rise in both the age and number of patient's requiring treatment, due in part to an aging population and expanded anticoagulation use. However, limited data and conflicting conclusions exist on extreme-aged geriatric patients (≥ 85 years of age) after undergoing surgery. Patients undergoing SDH evacuation at a tertiary academic medical center between November 2013-December 2021 were retrospectively identified. The study group consisted of patients ≥ 85 years (Group 1) diagnosed with a chronic SDH surgically evacuated. A control group was created matching patients by 70-84 years of age, gender, and anticoagulation use (Group 2). Multiple metrics were evaluated between the two including length-of hospital-stay, tracheostomy/PEG placement, reoperation rate, complications, discharge location, neurological outcome at the time of discharge, and survival. A total of 130 patients were included; 65 in Group 1 and 65 in Group 2. Patient demographics, medical comorbidities, SDH characteristics, international normalized ratio, partial thromboplastin time, and use of blood thinning agents were similar between the two groups. Kaplan Meier survival analysis at one-year was 80% for Group 1 and 76% for Group 2. No significant difference was identified using the log-rank test for equality of survivor functions (p = 0.26). All measured outcomes including GCS at time of discharge, length of stay, rate of reoperations, and neurological outcome were statistically similar between the two groups. Backwards stepwise conditional logistic regression revealed no significant association between poor outcomes at the time of discharge and age. Alternatively, anticoagulation use was found to be associated with poor outcomes (OR 3.55, 95% CI 1.08-11.60; p = 0.036). Several outcome metrics and statistical analyses were used to compare patients ≥ 85 years of age to younger geriatric patients (70-84 years) in a matched cohort study. Adjusting for age group, gender, and anticoagulation use, no significant difference was found between the two groups including neurological outcome at discharge, reoperation rate, and survival.

Transplantation of human neural progenitor cells secreting GDNF into the spinal cord of patients with ALS: a phase 1/2a trial.

Amyotrophic lateral sclerosis (ALS) involves progressive motor neuron loss, leading to paralysis and death typically within 3-5 years of diagnosis. Dysfunctional astrocytes may contribute to disease and glial cell line-derived neurotrophic factor (GDNF) can be protective. Here we show that human neural progenitor cells transduced with GDNF (CNS10-NPC-GDNF) differentiated to astrocytes protected spinal motor neurons and were safe in animal models. CNS10-NPC-GDNF were transplanted unilaterally into the lumbar spinal cord of 18 ALS participants in a phase 1/2a study (NCT02943850). The primary endpoint of safety at 1 year was met, with no negative effect of the transplant on motor function in the treated leg compared with the untreated leg. Tissue analysis of 13 participants who died of disease progression showed graft survival and GDNF production. Benign neuromas near delivery sites were common incidental findings at post-mortem. This study shows that one administration of engineered neural progenitors can provide new support cells and GDNF delivery to the ALS patient spinal cord for up to 42 months post-transplantation.

A Phase I Study of Autologous Dendritic Cell Vaccine Pulsed with Allogeneic Stem-like Cell Line Lysate in Patients with Newly Diagnosed or Recurrent Glioblastoma.

PURPOSE: Glioblastoma (GBM) is a heterogeneous malignancy with multiple subpopulations of cancer cells present within any tumor. We present the results of a phase I clinical trial using an autologous dendritic cell (DC) vaccine pulsed with lysate derived from a GBM stem-like cell line. PATIENTS AND METHODS: Patients with newly diagnosed and recurrent GBM were enrolled as separate cohorts. Eligibility criteria included a qualifying surgical resection or minimal tumor size, ≤ 4-mg dexamethasone daily dose, and Karnofsky score ≥70. Vaccine treatment consisted of two phases: an induction phase with vaccine given weekly for 4 weeks, and a maintenance phase with vaccines administered every 8 weeks until depletion of supply or disease progression. Patients with newly diagnosed GBM also received standard-of-care radiation and temozolomide. The primary objective for this open-label, single-institution trial was to assess the safety and tolerability of the autologous DC vaccine. RESULTS: For the 11 patients with newly diagnosed GBM, median progression-free survival (PFS) was 8.75 months, and median overall survival was 20.36 months. For the 25 patients with recurrent GBM, median PFS was 3.23 months, 6-month PFS was 24%, and median survival was 11.97 months. A subset of patients developed a cytotoxic T-cell response as determined by an IFNγ ELISpot assay. CONCLUSIONS: In this trial, treatment of newly diagnosed and recurrent GBM with autologous DC vaccine pulsed with lysate derived from an allogeneic stem-like cell line was safe and well tolerated. Clinical outcomes add to the body of evidence suggesting that immunotherapy plays a role in the treatment of GBM.

Early versus delayed postoperative radiotherapy for treatment of low-grade gliomas.

BACKGROUND: This is an update of the review originally published in 2011 and first updated in 2015. In most people with low-grade gliomas (LGG), the primary treatment regimen remains a combination of surgery followed by postoperative radiotherapy. However, the optimal timing of radiotherapy is controversial. It is unclear whether to use radiotherapy in the early postoperative period, or whether radiotherapy should be delayed until tumour progression occurs. OBJECTIVES: To assess the effects of early postoperative radiotherapy versus radiotherapy delayed until tumour progression for low-grade intracranial gliomas in people who had initial biopsy or surgical resection. SEARCH METHODS: Original searches were run up to September 2014. An updated literature search from September 2014 through November 2019 was performed on the following electronic databases: the Cochrane Central Register of Controlled Trials (CENTRAL; 2019, Issue 11), MEDLINE via Ovid (September 2014 to November week 2 2019), and Embase via Ovid (September 2014 to 2019 week 46) to identify trials for inclusion in this Cochrane review update. SELECTION CRITERIA: We included randomised controlled trials (RCTs) that compared early versus delayed radiotherapy following biopsy or surgical resection for the treatment of people with newly diagnosed intracranial LGG (astrocytoma, oligodendroglioma, mixed oligoastrocytoma, astroblastoma, xanthoastrocytoma, or ganglioglioma). Radiotherapy may include conformal external beam radiotherapy (EBRT) with linear accelerator or cobalt-60 sources, intensity-modulated radiotherapy (IMRT), or stereotactic radiosurgery (SRS). DATA COLLECTION AND ANALYSIS: Three review authors independently assessed the trials for inclusion and risk of bias, and extracted study data. We resolved any differences between review authors by discussion. Adverse effects were also extracted from the study report. We performed meta-analyses using a random-effects model with inverse variance weighting. MAIN RESULTS: We included one large, multi-institutional, prospective RCT, involving 311 participants; the risk of bias in this study was unclear. This study found that early postoperative radiotherapy was associated with an increase in time to progression compared to observation (and delayed radiotherapy upon disease progression) for people with LGG but did not significantly improve overall survival (OS). The median progression-free survival (PFS) was 5.3 years in the early radiotherapy group and 3.4 years in the delayed radiotherapy group (hazard ratio (HR) 0.59, 95% confidence interval (CI) 0.45 to 0.77; P < 0.0001; 311 participants; 1 trial; low-quality evidence). The median OS in the early radiotherapy group was 7.4 years, while the delayed radiotherapy group experienced a median overall survival of 7.2 years (HR 0.97, 95% CI 0.71 to 1.33; P = 0.872; 311 participants; 1 trial; low-quality evidence). The total dose of radiotherapy given was 54 Gy; five fractions of 1.8 Gy per week were given for six weeks. Adverse effects following radiotherapy consisted of skin reactions, otitis media, mild headache, nausea, and vomiting. Rescue therapy was provided to 65% of the participants randomised to delayed radiotherapy. People in both cohorts who were free from tumour progression showed no differences in cognitive deficit, focal deficit, performance status, and headache after one year. However, participants randomised to the early radiotherapy group experienced significantly fewer seizures than participants in the delayed postoperative radiotherapy group at one year (25% versus 41%, P = 0.0329, respectively). AUTHORS' CONCLUSIONS: Given the high risk of bias in the included study, the results of this analysis must be interpreted with caution. Early radiation therapy was associated with the following adverse effects: skin reactions, otitis media, mild headache, nausea, and vomiting. People with LGG who underwent early radiotherapy showed an increase in time to progression compared with people who were observed and had radiotherapy at the time of progression. There was no significant difference in overall survival between people who had early versus delayed radiotherapy; however, this finding may be due to the effectiveness of rescue therapy with radiation in the control arm. People who underwent early radiation had better seizure control at one year than people who underwent delayed radiation. There were no cases of radiation-induced malignant transformation of LGG. However, it remained unclear whether there were differences in memory, executive function, cognitive function, or quality of life between the two groups since these measures were not evaluated.

Phase 1 Safety, Pharmacokinetics, and Fluorescence Imaging Study of Tozuleristide (BLZ-100) in Adults With Newly Diagnosed or Recurrent Gliomas.

BACKGROUND: Fluorescence-guided surgery (FGS) can improve extent of resection in gliomas. Tozuleristide (BLZ-100), a near-infrared imaging agent composed of the peptide chlorotoxin and a near-infrared fluorophore indocyanine green, is a candidate molecule for FGS of glioma and other tumor types. OBJECTIVE: To perform a phase 1 dose-escalation study to characterize the safety, pharmacokinetics, and fluorescence imaging of tozuleristide in adults with suspected glioma. METHODS: Patients received a single intravenous dose of tozuleristide 3 to 29 h before surgery. Fluorescence images of tumor and cavity in Situ before and after resection and of excised tissue ex Vivo were acquired, along with safety and pharmacokinetic measures. RESULTS: A total of 17 subjects received doses between 3 and 30 mg. No dose-limiting toxicity was observed, and no reported adverse events were considered related to tozuleristide. At doses of 9 mg and above, the terminal serum half-life for tozuleristide was approximately 30 min. Fluorescence signal was detected in both high- and low-grade glial tumors, with high-grade tumors generally showing greater fluorescence intensity compared to lower grade tumors. In high-grade tumors, signal intensity increased with increased dose levels of tozuleristide, regardless of the time of dosing relative to surgery. CONCLUSION: These results support the safety of tozuleristide at doses up to 30 mg and suggest that tozuleristide imaging may be useful for FGS of gliomas.

A Simple Three-dimensional Hydrogel Platform Enables Ex Vivo Cell Culture of Patient and PDX Tumors for Assaying Their Response to Clinically Relevant Therapies.

A cell culture platform that enables ex vivo tissue growth from patients or patient-derived xenograft (PDX) models and assesses sensitivity to approved therapies (e.g., temozolomide) in a clinically relevant time frame would be very useful in translational research and personalized medicine. Here, we present a novel three-dimensional (3D) ECM hydrogel system, VersaGel, for assaying ex vivo growth and therapeutic response with standard image microscopy. Specifically, multicellular spheroids deriving from either 5 patients with glioblastoma (GBM) or a renal cell carcinoma (RCC) PDX model were incorporated into VersaGel and treated with temozolomide and several other therapies, guided by the most recent advances in GBM treatment. RCC ex vivo tissue displayed invasive phenotypes in conditioned media. For the GBM patient tumor testing, all five clinical responses were predicted by the results of our 3D-temozolomide assay. In contrast, the MTT assay found no response to temozolomide regardless of the clinical outcome, and moreover, basement membrane extract failed to predict the 2 patient responders. Finally, 1 patient was tested with repurposed drugs currently being administered in GBM clinical trials. Interestingly, IC50s were lower than C max for crizotinib and chloroquine, but higher for sorafenib. In conclusion, a novel hydrogel platform, VersaGel, enables ex vivo tumor growth of patient and PDX tissue and offers insight into patient response to clinically relevant therapies. We propose a novel 3D hydrogel platform, VersaGel, to grow ex vivo tissue (patient and PDX) and assay therapeutic response using time-course image analysis.

Blockade of a Laminin-411-Notch Axis with CRISPR/Cas9 or a Nanobioconjugate Inhibits Glioblastoma Growth through Tumor-Microenvironment Cross-talk.

There is an unmet need for the treatment of glioblastoma multiforme (GBM). The extracellular matrix, including laminins, in the tumor microenvironment is important for tumor invasion and progression. In a panel of 226 patient brain glioma samples, we found a clinical correlation between the expression of tumor vascular laminin-411 (α4ß1γ1) with higher tumor grade and with expression of cancer stem cell (CSC) markers, including Notch pathway members, CD133, Nestin, and c-Myc. Laminin-411 overexpression also correlated with higher recurrence rate and shorter survival of GBM patients. We also showed that depletion of laminin-411 α4 and ß1 chains with CRISPR/Cas9 in human GBM cells led to reduced growth of resultant intracranial tumors in mice and significantly increased survival of host animals compared with mice with untreated cells. Inhibition of laminin-411 suppressed Notch pathway in normal and malignant human brain cell types. A nanobioconjugate potentially suitable for clinical use and capable of crossing blood-brain barrier was designed to block laminin-411 expression. Nanobioconjugate treatment of mice carrying intracranial GBM significantly increased animal survival and inhibited multiple CSC markers, including the Notch axis. This study describes an efficient strategy for GBM treatment via targeting a critical component of the tumor microenvironment largely independent of heterogeneous genetic mutations in glioblastoma.Significance: Laminin-411 expression in the glioma microenvironment correlates with Notch and other cancer stem cell markers and can be targeted by a novel, clinically translatable nanobioconjugate to inhibit glioma growth.

Hispanic and African American adult brain tumor patients treated at Harbor-UCLA Medical Center compared to Los Angeles County and Torrance, California.

The objective of this study is to shed light on racial disparities among Hispanic and African American adult brain tumor patients treated at Harbor-UCLA Medical Center compared to the general populations of Los Angeles County (LAC) and Torrance, California (CA). A retrospective review of patients admitted to the neurosurgery service at Harbor-UCLA Medical Center during years 2006 through 2010 was performed. Government census data was queried and pertinent national statistics were retrieved. Brain tumor patients at Harbor-UCLA were compared to the general populations of LAC and Torrance. A total of 271 patients were included in the study. The mean age was 46.9 years. Hispanics comprised the majority of neurosurgical patients (n = 151, 55.7%), followed by African Americans (n = 35, 12.9%). A greater percentage of Hispanic patients were treated at Harbor-UCLA relative to the general Hispanic populations of LAC and Torrance (p < .001). A greater percentage of African American patients were treated at Harbor-UCLA relative to the general African American populations of LAC and Torrance (p = .035 and p < .001, respectively). Our data revealed significant racial disparities amid the Harbor-UCLA Hispanic and African American patient populations compared to the general Angeleno populations of LAC and Torrance.

Whole brain radiation therapy (WBRT) alone versus WBRT and radiosurgery for the treatment of brain metastases.

BACKGROUND: Historically, whole brain radiation therapy (WBRT) has been the main treatment for brain metastases. Stereotactic radiosurgery (SRS) delivers high-dose focused radiation and is being increasingly utilized to treat brain metastases. The benefit of adding SRS to WBRT is unclear. This is an updated version of the original Cochrane Review published in Issue 9, 2012. OBJECTIVES: To assess the efficacy of WBRT plus SRS versus WBRT alone in the treatment of adults with brain metastases. SEARCH METHODS: For the original review, in 2009 we searched the following electronic databases: CENTRAL, MEDLINE, Embase, and CancerLit in order to identify trials for inclusion in this review. For the first update the searches were updated in May 2012.For this update, in May 2017 we searched CENTRAL, MEDLINE, and Embase in order to identify trials for inclusion in the review. SELECTION CRITERIA: We restricted the review to randomized controlled trials (RCTs) that compared use of WBRT plus SRS versus WBRT alone for upfront treatment of adults with newly diagnosed metastases (single or multiple) in the brain resulting from any primary, extracranial cancer. DATA COLLECTION AND ANALYSIS: We used the generic inverse variance method, random-effects model in Review Manager 5 for the meta-analysis. MAIN RESULTS: We identified three studies and one abstract for inclusion but we could only include two studies, with a total of 358 participants in a meta-analysis. This found no difference in overall survival (OS) between the WBRT plus SRS and WBRT alone groups (hazard ratio (HR) 0.82, 95% confidence interval (CI) 0.65 to 1.02; 2 studies, 358 participants; moderate-quality evidence). For participants with one brain metastasis median survival was significantly longer in the WBRT plus SRS group (6.5 months) versus WBRT group (4.9 months; P = 0.04). Participants in the WBRT plus SRS group had decreased local failure compared to participants who received WBRT alone (HR 0.27, 95% CI 0.14 to 0.52; 2 studies, 129 participants; moderate-quality evidence). Furthermore, we observed an improvement in performance status scores and decrease in steroid use in the WBRT plus SRS group (risk ratio (RR) 0.64 CI 0.42 to 0.97; 1 study, 118 participants; low-quality evidence). Unchanged or improved Karnofsky Performance Scale (KPS) at six months was seen in 43% of participants in the combined therapy group versus only 28% in the WBRT-alone group (RR 0.78 CI 0.61 to 1.00; P value = 0.05; 1 study, 118 participants; low-quality evidence). Overall, risk of bias in the included studies was unclear. AUTHORS' CONCLUSIONS: Since the last version of this review we have identified one new study that met the inclusion criteria. However, due to a lack of data from this study we were not able to include it in a meta-analysis. Given the unclear risk of bias in the included studies, the results of this analysis have to be interpreted with caution. In our analysis of all included participants, SRS plus WBRT did not show a survival benefit over WBRT alone. However, performance status and local control were significantly better in the SRS plus WBRT group. Furthermore, significantly longer OS was reported in the combined treatment group for recursive partitioning analysis (RPA) Class I patients as well as patients with single metastasis. Most of our outcomes of interest were graded as moderate-quality evidence according to the GRADE criteria and the risk of bias in the majority of included studies was mostly unclear.

Biopsy versus resection for the management of low-grade gliomas.

BACKGROUND: This is an updated version of the original Cochrane review published in 2013, Issue 4.Low-grade gliomas (LGG) constitute a class of slow-growing primary brain neoplasms. Patients with clinically and radiographically suspected LGG have two initial surgical options, biopsy or resection. Biopsy can provide a histological diagnosis with minimal risk but does not offer a direct treatment. Resection may have additional benefits such as increasing survival and delaying recurrence, but is associated with a higher risk for surgical morbidity. There remains controversy about the role of biopsy versus resection and the relative clinical outcomes for the management of LGG. OBJECTIVES: To assess the clinical effectiveness of biopsy compared to surgical resection in patients with a new lesion suspected to be a LGG. SEARCH METHODS: The following electronic databases were searched in 2012 for the first version of the review: Cochrane Central Register of Controlled Trials (CENTRAL) (2012, Issue 11), MEDLINE (1950 to November week 3 2012), Embase (1980 to Week 46 2012). For this updated version, the following electronic databases were searched: Cochrane Central Register of Controlled Trials (CENTRAL) (2016, Issue 5), MEDLINE (Nov 2012 to June week 3 2016), Embase (Nov 2012 to 2016 week 26). All relevant articles were identified on PubMed and by using the 'related articles' feature. We also searched unpublished and grey literature including ISRCTN-metaRegister of Controled Trials, Physicians Data Query and ClinicalTrials.gov for ongoing trials. SELECTION CRITERIA: We planned to include patients of any age with a suspected intracranial LGG receiving biopsy or resection within a randomized clinical trial (RCT) or controlled clinical trial (CCT). Patients with prior resections, radiation therapy, or chemotherapy for LGG were excluded. Outcome measures included overall survival (OS), progression-free survival (PFS), functionally independent survival (FIS), adverse events, symptom control, and quality of life (QoL). DATA COLLECTION AND ANALYSIS: A total of 1375 updated citations were searched and critically analyzed for relevance. This was undertaken independently by two review authors. The original electronic database searches yielded a total of 2764 citations. In total, 4139 citations have been critically analyzed for this updated review. MAIN RESULTS: No new RCTs of biopsy or resection for LGG were identified. No additional ineligible non-randomized studies (NRS) were included in this updated review. Twenty other ineligible studies were previously retrieved for further analysis despite not meeting the pre-specified criteria. Ten studies were retrospective or were literature reviews. Three studies were prospective, however they were limited to tumor recurrence and volumetric analysis and extent of resection. One study was a population-based parallel cohort in Norway, but not an RCT. Four studies were RCTs, however patients were randomized with respect to varying radiotherapy regimens to assess timing and dose of radiation. One RCT was on high-grade gliomas (HGGs) and not LGG. Finally, one RCT evaluated diffusion tensor imaging (DTI)-based neuro-navigation for surgical resection. AUTHORS' CONCLUSIONS: Since the last version of this review, no new studies have been identified for inclusion and currently there are no RCTs or CCTs available on which to base definitive clinical decisions. Therefore, physicians must approach each case individually and weigh the risks and benefits of each intervention until further evidence is available. Some retrospective studies and non-randomized prospective studies do seem to suggest improved OS and seizure control correlating to higher extent of resection. Future research could focus on RCTs to determine outcomes benefits for biopsy versus resection.

Adjuvant Radiosurgery Versus Serial Surveillance Following Subtotal Resection of Atypical Meningioma: A Systematic Analysis.

BACKGROUND: Atypical meningioma (AM) is an aggressive subtype of meningioma associated with a high recurrence rates (RR) following surgical resection. Recent studies have compared outcomes of various treatment strategies, but advantages of adjuvant radiosurgery (ARS) over serial surveillance (SS) following subtotal resection (STR) remain unclear. To further elucidate this issue, we systematically analyzed the current literature on AM and compared outcomes of ARS versus SS after STR. METHODS: Embase, PubMed, and Cochrane databases were queried using relevant search terms. Retrospective case series that described patients with AM treated with ARS and SS after STR were included. Tests of proportions were performed to detect significant variations in RR, 5-year progression-free survival (PFS), and 5-year overall survival (OS) between the treatment strategies (ARS vs. SS) and among individual studies. RESULTS: A total of 619 patients (263 in the ARS group and 356 in the SS group) were identified. Mean RR, 5-year PFS, and 5-year OS were 53.5%, 50.3%, and 74.9%, respectively, for ARS versus 89.8%, 19.1%, and 89.8% for SS. RR differed between treatment strategies and ARS studies (P < 0.001), and 5-year PFS differed among treatment strategies, ARS, and SS studies (P < 0.001, P = 0.007, and P < 0.001, respectively). CONCLUSIONS: The data presented here show significant differences in RR and 5-year PFS between ARS and SS, suggesting a potential benefit of ARS. As our understanding of the clinical outcomes of various treatment strategies for AM increases, we also move closer to integrating modalities, such as radiosurgery, into management guidelines.

Real time optical Biopsy: Time-resolved Fluorescence Spectroscopy instrumentation and validation.

The Time-resolved fluorescence spectroscopy (TR-FS) has the potential to differentiate tumor and normal tissue in real time during surgical excision. In this manuscript, we describe the design of a novel TR-FS device, along with preliminary data on detection accuracy for fluorophores in a mixture. The instrument is capable of near real-time fluorescence lifetime acquisition in multiple spectral bands and analysis. It is also able to recover fluorescence lifetime with sub-20ps accuracy as validated with individual organic fluorescence dyes and dye mixtures yielding lifetime values for standard fluorescence dyes that closely match with published data. We also show that TR-FS is able to quantify the relative concentration of fluorescence dyes in a mixture by the unmixing of lifetime decays. We show that the TR-FS prototype is able to identify in near-real time the concentrations of dyes in a complex mixture based on previously trained data. As a result, we demonstrate that in complex mixtures of fluorophores, the relative concentration information is encoded in the fluorescence lifetime across multiple spectral bands. We show for the first time the temporal and spectral measurements of a mixture of fluorochromes and the ability to differentiate relative concentrations of each fluorochrome mixture in real time.

Congress of Neurological Surgeons Systematic Review and Evidence-Based Guideline on Preoperative Imaging Assessment of Patients With Suspected Nonfunctioning Pituitary Adenomas.

BACKGROUND: The authors reviewed published articles pertaining to the preoperative imaging evaluation of nonfunctioning pituitary adenomas (NFPAs) and formulated recommendations. OBJECTIVE: To provide an exhaustive review of published articles pertaining to the preoperative imaging evaluation of nonfunctioning pituitary adenomas. METHODS: The MEDLINE database was queried for studies investigating imaging for the preoperative evaluation of pituitary adenomas. RESULTS: From an initial search of 5598 articles, 122 articles were evaluated in detail and included in this article. Based on analysis of these articles, the recommendations are as follows: (1) High-resolution magnetic resonance imaging (level II) is recommended as the standard for preoperative assessment of nonfunctioning pituitary adenomas, but may be supplemented with CT (level III) and fluoroscopy (level III). (2) Although there are promising results suggesting the utility of magnetic resonance spectroscopy, magnetic resonance perfusion, positron emission tomography, and single-photon emission computed tomography, there is insufficient evidence to make formal recommendations pertaining to their clinical applications. CONCLUSION: The authors identified 122 articles that form the basis of recommendations for preoperative imaging evaluation of nonfunctioning pituitary adenomas. The full guidelines document for this chapter can be located at https://www.cns.org/guidelines/guidelines-management-patients-non-functioning-pituitary-adenomas/Chapter_2. ABBREVIATIONS: CT, computed tomographyDWI, diffusion-weighted imagingMRI, magnetic resonance imagingNFPA, nonfunctioning pituitary adenoma.

Congress of Neurological Surgeons Systematic Review and Evidence-Based Guideline for Pretreatment Endocrine Evaluation of Patients With Nonfunctioning Pituitary Adenomas.

BACKGROUND: Nonfunctioning pituitary adenomas (NFPAs) are among the most common pituitary lesions and may present with hypopituitarism and/or hyperprolactinemia. OBJECTIVE: To review the existing literature as it pertains to preoperative endocrine assessment in the workup for NFPAs. METHODS: A systematic review methodology was utilized to identify and screen articles assessing the role and results of preoperative laboratory assessment in patients with NFPAs. The prevalence of individual pituitary hormonal axis deficiencies was reviewed. RESULTS: Twenty-nine studies met inclusion criteria for analysis. No class I evidence was available, and all studies met criteria for class II evidence. Baseline serum laboratory assessment showed a prevalence of overall hypopituitarism in 37% to 85% of patients. The most common hormonal axis deficiency was growth hormone deficiency, prevalent in 61% to 100% of patients. The next most common deficit was hypogonadism, seen in 36% to 95% of patients. Adrenal insufficiency was diagnosed in 17% to 62% of patients. Finally, hypothyroidism was seen in 8% to 81% of patients. Hyperprolactinemia was seen in 25% to 65% of patients, with a mean level of 39 ng/mL and with a minority of patients exceeding a serum prolactin level of 200 ng/mL. No evidence supporting routine biomarker testing (eg, α-subunit or chromogranin A) or genetic testing in patients with sporadic NFPAs was available. CONCLUSION: Despite a paucity of class I evidence, multiple retrospective studies have demonstrated a high prevalence of hypopituitarism in patients with NFPAs. Routine endocrine analysis of all anterior pituitary axes to assess for hypopituitarism is recommended, with prolactin and insulin-like growth factor 1 evaluation also valuable to assess for hypersecretion states that might not be clinically suspected. The full guidelines document for this chapter can be located at https://www.cns.org/guidelines/guidelines-management-patients-non-functioning-pituitary-adenomas/Chapter_3. ABBREVIATIONS: GH, growth hormoneIGF-1, insulin-like growth factor 1NFPA, nonfunctioning pituitary adenoma.

Congress of Neurological Surgeons Systematic Review and Evidence-Based Guideline on Pretreatment Ophthalmology Evaluation in Patients With Suspected Nonfunctioning Pituitary Adenomas.

BACKGROUND: Nonfunctioning pituitary adenomas (NFPAs) are the most frequent pituitary tumors. Visual symptoms from NFPAs are common and include visual field defects, loss of central vision, and motility problems resulting in diplopia. OBJECTIVE: To create evidence-based guidelines in an attempt to formulate guidance for preoperative ophthalmologic evaluation of NFPA patients. METHODS: An extensive literature search was performed. Only clinical articles describing preoperative ophthalmologic evaluation of adult patients with NFPA were included. To ascertain the class of evidence for the posttreatment follow-up, the authors used the Clinical Assessment evidence-based classification. RESULTS: Six studies met the inclusion criteria with respect to the questions regarding the preoperative ophthalmologic evaluation of NFPA patients. Based on the studies located through the search, the authors formulated evidence-based recommendations as they pertain to the necessity of ophthalmologic evaluation before surgical treatment. CONCLUSION: Preoperative ophthalmologic evaluation is recommended. Such evaluation can provide prognostic factors for recovery and, when paired with postoperative evaluation, documents postoperative change. In addition to formal ophthalmologic examination, tests of value include automated static perimetry and optical coherence tomography. Older patients and patients with longer duration (>4 months) of vision loss should be counseled regarding the reduced chance of postoperative vision improvement. The full guidelines document for this chapter can be located at https://www.cns.org/guidelines/guidelines-management-patients-non-functioning-pituitary-adenomas/Chapter_4. ABBREVIATIONS: NFPA, nonfunctioning pituitary adenomaOCT, optical coherence tomography.

Congress of Neurological Surgeons Systematic Review and Evidence-Based Guideline on Primary Management of Patients With Nonfunctioning Pituitary Adenomas.

BACKGROUND: Nonfunctioning pituitary adenomas (NFPAs) are among the most common pituitary lesions and may present clinically with vision loss and hypopituitarism. OBJECTIVE: To characterize the existing literature as it pertains to the initial management of NFPAs. METHODS: A systematic literature review was conducted to identify and screen articles assessing primary treatment options (surgical, medical, radiation based, or observation) for NFPAs. Outcomes assessed included vision-, endocrine-, and headache-related symptoms, as well as tumor response to therapy. Twenty-five studies met inclusion criteria for analysis. RESULTS: A considerable amount of class II evidence (14 studies) was identified supporting primary surgical intervention in patients with symptomatic NFPA macroadenomas, resulting in immediate tumor volume reduction in nearly all patients and a residual tumor rate of 10% to 36%. One prospective, observational cohort study and multiple retrospective studies showed improved visual function in 75% to 91% of surgically treated patients and improved hypopituitarism in 35% to 50% of patients. Limited class II evidence showed inconsistent benefits for observation alone (1 study), primary radiation-based treatment (3 studies), or primary medical treatment (8 studies) for improving vision, headaches, hypopituitarism, or tumor volume. One retrospective study implementing observation alone showed tumor progression in 50% of patients and a requirement for surgery in 21% of patients. Eight studies assessing primary medical therapy for NFPAs showed inconsistent tumor response rates using somatostatin analogs (12%-40% response rate), dopamine agonist therapy (0%-61% response rate), or combination therapy (60% response rate). Three studies reporting primary radiosurgery for NFPAs showed decreased tumor size in 38% to 60% of patients. CONCLUSION: Multiple retrospective and some prospective studies have demonstrated consistent effectiveness of primary surgical resection of symptomatic NFPAs with acceptable morbidity rates. Limited and inconsistent reports are available for alternative treatment strategies, including radiation, medical treatment, and observation alone; these modalities may, however, play a valid role in patients who are not surgical candidates. Based on the available evidence, the authors recommend surgical resection as the preferred primary intervention for symptomatic NFPAs. The full guidelines document for this chapter can be located at https://www.cns.org/guidelines/guidelines-management-patients-non-functioning-pituitary-adenomas/Chapter_5. ABBREVIATION: NFPA, nonfunctioning pituitary adenoma.

Congress of Neurological Surgeons Systematic Review and Evidence-Based Guideline on Surgical Techniques and Technologies for the Management of Patients With Nonfunctioning Pituitary Adenomas.

BACKGROUND: Numerous technological adjuncts are used during transsphenoidal surgery for nonfunctioning pituitary adenomas (NFPAs), including endoscopy, neuronavigation, intraoperative magnetic resonance imaging (MRI), cerebrospinal fluid (CSF) diversion, and dural closure techniques. OBJECTIVE: To generate evidence-based guidelines for the use of NFPA surgical techniques and technologies. METHODS: An extensive literature search spanning January 1, 1966, to October 1, 2014, was performed, and only articles pertaining to technological adjuncts for NFPA resection were included. The clinical assessment evidence-based classification was used to ascertain the class of evidence. RESULTS: Fifty-six studies met the inclusion criteria, and evidence-based guidelines were formulated on the use of endoscopy, neuronavigation, intraoperative MRI, CSF diversion, and dural closure techniques. CONCLUSION: Both endoscopic and microscopic transsphenoidal approaches are recommended for symptom relief in patients with NFPAs, with the extent of tumor resection improved by adequate bony exposure and endoscopic visualization. In select cases, combined transcranial and transsphenoidal approaches are recommended. Although intraoperative MRI can improve gross total resection, its use is associated with an increased false-positive rate and is thus not recommended. There is insufficient evidence to recommend the use of neuronavigation, CSF diversion, intrathecal injection, or specific dural closure techniques. The full guidelines document for this chapter can be located at https://www.cns.org/guidelines/guidelines-management-patients-non-functioning-pituitary-adenomas/Chapter_6. ABBREVIATIONS: CSF, cerebrospinal fluidNFPA, nonfunctioning pituitary adenoma.

Congress of Neurological Surgeons Systematic Review and Evidence-Based Guideline for the Management of Patients With Residual or Recurrent Nonfunctioning Pituitary Adenomas.

BACKGROUND: Despite the advancement of microsurgical and endoscopic techniques, some nonfunctioning pituitary adenomas (NFPAs) can be difficult to cure. Tumor recurrence or incomplete resection may occur in some patients with NFPAs, and management strategies for these NFPAs remain unclear. OBJECTIVE: To review the existing literature as it pertains to the management of postsurgical residual or recurrent NFPAs. METHODS: A systematic review of the treatment options for residual or recurrent NFPAs was performed. In this review, the authors critically evaluated the evidence to support the options of repeat microsurgical resection, stereotactic radiosurgery (SRS), stereotactic radiotherapy (SRT), and fractionated radiation therapy (XRT). RESULTS: Forty-nine studies met the inclusion criteria for analysis: outcome of repeat surgical resection (n = 4), radiosurgery (ie, single-session or hypofractionated SRS; n = 24), or fractionated radiotherapy (ie, conventional XRT, proton beam radiotherapy, intensity-modulated radiotherapy, SRT; n = 21). No class I evidence was available; 6 studies met criteria for class II evidence; and other studies provided class III evidence. A meta-analysis of 5 class II studies with recurrence rates for both adjuvant radiation therapy and observation demonstrated that XRT for residual/recurrent NFPAs offered a lower rate of recurrence (odds ratio = 0.04; 95% confidence interval, 0.01-0.20; P < .001). The analysis also demonstrated significant heterogeneity between the included studies (χ = 20.70; P = .003; I = 81%). CONCLUSION: Repeat resection, SRS, SRT, and XRT play a role in the management of patients with recurrent or residual NFPAs. SRS or some type of radiation therapy is typically performed for patients with residual tumor or tumor recurrence after resection. The full guidelines document for this chapter can be located at https://www.cns.org/guidelines/guidelines-management-patients-non-functioning-pituitary-adenomas/Chapter_7. ABBREVIATIONS: NFPA, nonfunctioning pituitary adenomaSRS, stereotactic radiosurgerySRT, stereotactic radiotherapyXRT, fractionated radiation therapy.

Congress of Neurological Surgeons Systematic Review and Evidence-Based Guideline on Posttreatment Follow-up Evaluation of Patients With Nonfunctioning Pituitary Adenomas.

BACKGROUND: Nonfunctioning pituitary adenomas (NFPAs) are the most frequent pituitary tumors. Due to the lack of hormonal hypersecretion, posttreatment follow-up evaluation of NFPAs is challenging. OBJECTIVE: To create evidence-based guidelines in an attempt to formulate guidance for posttreatment follow-up in a consistent, rigorous, and cost-effective way. METHODS: An extensive literature search was performed. Only clinical articles describing postoperative follow-up of adult patients with NFPAs were included. To ascertain the class of evidence for the posttreatment follow-ups, the authors used the Clinical Assessment evidence-based classification. RESULTS: Twenty-three studies met the inclusion criteria with respect to answering the questions on the posttreatment radiologic, endocrinologic, and ophthalmologic follow-up. Through this search, the authors formulated evidence-based guidelines for radiologic, endocrinologic, and ophthalmologic follow-up after surgical and/or radiation treatment. CONCLUSION: Long-term radiologic, endocrinologic, and ophthalmologic surveillance monitoring after surgical and/or radiation therapy treatment of NFPAs to evaluate for tumor recurrence or regrowth, as well as pituitary and visual status, is recommended. There is insufficient evidence to make a recommendation on the duration of time of surveillance and its frequency. It is recommended that the first radiologic study to evaluate the extent of resection of the NFPA be performed ≥3 months after surgical intervention. The full guidelines document for this chapter can be located at https://www.cns.org/guidelines/guidelines-management-patients-non-functioning-pituitary-adenomas/Chapter_8. ABBREVIATION: NFPA, nonfunctioning pituitary adenoma.

A national perspective of adult gangliogliomas.

Gangliogliomas (GG) are rare tumors of the nervous system. Patient characteristics and clinical outcomes of low and high-grade GG have been difficult to elucidate in the adult population. This study aims to further elaborate on GG treatment and overall survival utilizing a larger cohort than previously published. The USA National Cancer Database was utilized to evaluate adult (age 18years and older) patients diagnosed with GG between 2004 and 2006. Descriptive statistics and Kaplan-Meier overall survival estimates were provided. A total of 198 adult GG patients were diagnosed between 2004 and 2006. Of these, 181 (91.4%) were low-grade and 17 (8.6%) high-grade GG. Overall, the median age was 36years; approximately 50% of patients were female, and 86.5% Caucasian. Most patients (59%) had near/gross total resection. Radiation and chemotherapy were prescribed in 18 (9.1%) and 11 (5.7%) patients, respectively. Radiation (64.7% versus 3.9%, p<.0001) and chemotherapy (47.1% versus 1.7%, p<.0001) were more frequently given to patients with high-grade tumors than low-grade. The median overall survival of high-grade GG was 44.4months (95% confidence interval [CI]: 10.5-92.5) while the corresponding estimate for low-grade tumors was not reached. Older age (hazard ratio [HR] 1.72, 95% CI: 1.26-2.34) and high tumor grade (HR 3.91, 95% CI: 1.43-10.8) were found to be associated with poor survival. Adult GG have a temporal lobe predilection and overall gross total resection rate of 59%. Older patients with high-grade tumors had an increased hazard of mortality. High-grade GG were significantly more likely to be treated with radiation therapy and chemotherapy.