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Cranioplasty is a neurosurgical procedure that repairs a defect in the skull Coupled with the underlying pathology cranioplasty associated morbidity can have a large impact on patient quality of life, which is often poorly explored. The objective of this systematic review was to identify patient-reported outcomes evaluating health-related quality of life following cranioplasty. The review protocol was registered on PROSPERO (CRD42021251543) and a systematic review was conducted in accordance with the PRISMA statement. PubMed, Embase, CINAHL Plus, and the Cochrane databases were searched from inception to 1 May 2022. All studies reporting HRQoL following cranioplasty were included. Reporting was assessed using the ISOQOL checklist and risk of bias was assessed using the Newcastle-Ottawa Scale or the Johanna-Briggs Institute Scale, as appropriate. A total of 25 studies were included of which 20 were cross-sectional and 2 longitudinal. Most studies utilized study specific questionnaires and Likert scales to assess HRQoL. The studies found a significant improvement in physical functioning, social functioning, cosmetic outcome, and overall HRQoL following cranioplasty. Further longitudinal studies utilising validated measurement tools are required to better understand the effect of cranioplasty at a patient level.

Cranioplasty is an operation that aims to repair a defect in the skull. Indications commonly include Traumatic Brain Injury (TBI), tumours, and infections. It carries a high rate of postoperative morbidity. Due to underlying pathology and the nature of the operation patients' Health-related Quality of life (QoL) can be severely affected. Patient reported outcomes (PROs) are poorly understood following cranioplasty. To investigate PROs following cranioplasty a cross-sectional cohort study of adults undergoing cranioplasty between 01/03/2010-30/08/2020 was conducted. If consent was provided, participants were sent five health reporting questionnaires: a study specific questionnaire, EuroQoL - 5D - 5L (EQ-5D-5L), RAND Short-Form 36 (SF-36), Hospital Anxiety and Depression Scale (HADS), and Derriford Appearance Scale (DAS-24). 239 eligible patients were contacted and 72 (30.8%) participated. Median [Range] age was 52.5 [23 - 95] of which 59.7% (n= 43) were male. 16.9% (n = 12) were categorised with borderline and 29.0% (n = 20) with extreme depression, 15.9% (n = 11) reported borderline and 35.2% (n = 25) extreme anxiety. 69.1% (n = 47) had problems with usual activities and 71.6% (n = 49) suffered from pain/discomfort. Median (Range) EQ-5D-5L visual analogue scale score for overall health was 70.0 (5-100). 76.0% (n = 53) reported feeling conscious or having negative feelings towards their appearance. When compared to normative UK population, physical functioning, overall health, and energy/fatigue were the most affected. After cranioplasty, patients may have reduced HRQoL. Signposting and referral to well-being services could benefit patients' care. Adequately powered longitudinal studies are required to further elucidate change in PROs following cranioplasty., Competing Interests: Declarations. Ethical approval: This was a single centre, cross-sectional observational study carried out at The Walton Centre National Health Service (NHS) Foundation Trust, Liverpool, United Kingdom. Local audit approval was obtained prior to conducting the study. Additionally, this study was approved by the Research Ethics Committee of the NHS Health Research Authority (IRAS: 291914). Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Background: Tectal plate gliomas (TPGs) are a heterogeneous group of uncommon brain tumors. TPGs are considered indolent and are usually managed conservatively but they have the potential to transform into higher-grade tumors. The aims of this study were to investigate the natural history of adult TPG, treatment outcomes, and overall survival., Methods: A retrospective cohort analysis was performed of adult patients with TPG between 1993 and 2021. Baseline clinical, radiologic, and management characteristics were collected. The primary outcome was tumor progression, defined as increasing size on radiologic assessment or new gadolinium contrast enhancement. Secondary outcomes included management and mortality., Results: Thirty-nine patients were included, of whom 23 (52.2%) were men. Median age at diagnosis was 35 years (interquartile range, 27-53). Radiologic tumor progression was observed in 8 patients (20.5%). The 10-year progression-free survival was 72.6% (95% confidence interval [CI], 0.58-0.91). The 10-year overall survival was 86.5% (95% confidence interval, 0.75-1.0). Cerebrospinal fluid diversion procedures were used in 62% of the cohort (n = 24). Seventeen patients (43.6%) underwent at least 1 endoscopic third ventriculostomy, whereas only 6 patients (15.4%) underwent at least 1 ventriculoperitoneal shunt., Conclusions: TPG has an overall favorable clinical prognosis, although progression occurs in 1 in 5 patients. Showing accurate factors by which patients with TPG may be risk stratified should be a key area of further research. A follow-up duration of 10 years would be a reasonable window based on the radiologic progression rates in this study; however, larger cohort studies are needed to answer both questions definitively., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: The clinical management of patients with incidental intracranial meningioma varies markedly and is often based on clinician choice and observational data. Heterogeneous outcome measurement has likely hampered knowledge progress by preventing comparative analysis of similar cohorts of patients. This systematic review aimed to summarize the outcomes measured and reported in observational studies., Methods: A systematic literature search was performed to identify published full texts describing active monitoring of adult cohorts with incidental and untreated intracranial meningioma (PubMed, EMBASE, MEDLINE, and CINAHL via EBSCO, completed January 24, 2022). Reported outcomes were extracted verbatim, along with an associated definition and method of measurement if provided. Verbatim outcomes were de-duplicated and the resulting unique outcomes were grouped under standardized outcome terms. These were classified using the taxonomy proposed by the "Core Outcome Measures in Effectiveness Trials" (COMET) initiative., Results: Thirty-three published articles and 1 ongoing study were included describing 32 unique studies: study designs were retrospective n  = 27 and prospective n  = 5. In total, 268 verbatim outcomes were reported, of which 77 were defined. Following de-duplication, 178 unique verbatim outcomes remained and were grouped into 53 standardized outcome terms. These were classified using the COMET taxonomy into 9 outcome domains and 3 core areas., Conclusions: Outcome measurement across observational studies of incidental and untreated intracranial meningioma is heterogeneous. The standardized outcome terms identified will be prioritized through an eDelphi survey and consensus meeting of key stakeholders (including patients), in order to develop a Core Outcome Set for use in future observational studies., Competing Interests: M.D.J. received a grant from the National Institute for Health Research Health Technology Assessment program for the Radiation versus Observation for Atypical Meningioma (ROAM) trial (NIHR ID: 12/173/14). M.D.J. and S.J.M. received a grant from the National Institute for Health Research Health Technology Assessment program for Surgeons Trial Of Prophylaxis for Epilepsy in seizure naïve patients with Meningioma (STOP’EM) (NIHR ID: NIHR129748). T.S. founded and leads the Anaplastic Meningioma International Consortium (AMiCo). T.S. and M.D.J. cofounded the British-Irish Meningioma Society (BIMS). A.G.M. is a National Institute for Health Research (NIHR) Senior Investigator and is also part-funded by NIHR ARC North West Coast. The views expressed in this article are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care. M.P. has received honoraria for lectures, consultation or advisory board participation from the following for-profit companies: Bayer, Bristol-Myers Squibb, Novartis, Gerson Lehrman Group (GLG), CMC Contrast, GlaxoSmithKline, Mundipharma, Roche, BMJ Journals, MedMedia, Astra Zeneca, AbbVie, Lilly, Medahead, Daiichi Sankyo, Sanofi, Merck Sharp & Dome, Tocagen, Adastra, Servier. M.W. has received research grants from Quercis and Versameb, and honoraria for lectures or advisory board participation or consulting from Bayer, Curevac, Medac, Novartis, Novocure, Orbus, Philogen, Roche and Sandoz., (© The Author(s) 2024. Published by Oxford University Press, the Society for Neuro-Oncology and the European Association of Neuro-Oncology.)

Background: Meningioma clinical trials have assessed interventions including surgery, radiotherapy, and pharmacotherapy. However, agreement does not exist on what, how, and when outcomes of interest should be measured. To do so would allow comparative analysis of similar trials. This systematic review aimed to summarize the outcomes measured and reported in meningioma clinical trials., Methods: Systematic literature and trial registry searches were performed to identify published and ongoing intracranial meningioma clinical trials (PubMed, Embase, Medline, CINAHL via EBSCO, and Web of Science, completed January 22, 2022). Reported outcomes were extracted verbatim, along with an associated definition and method of measurement if provided. Verbatim outcomes were deduplicated and the resulting unique outcomes were grouped under standardized outcome terms. These were classified using the taxonomy proposed by the "Core Outcome Measures in Effectiveness Trials" (COMET) initiative., Results: Thirty published articles and 18 ongoing studies were included, describing 47 unique clinical trials: Phase 2 n  = 33, phase 3 n  = 14. Common interventions included: Surgery n  = 13, radiotherapy n  = 8, and pharmacotherapy n  = 20. In total, 659 verbatim outcomes were reported, of which 84 were defined. Following de-duplication, 415 unique verbatim outcomes remained and were grouped into 115 standardized outcome terms. These were classified using the COMET taxonomy into 29 outcome domains and 5 core areas., Conclusions: Outcome measurement across meningioma clinical trials is heterogeneous. The standardized outcome terms identified will be prioritized through an eDelphi survey and consensus meeting of key stakeholders (including patients), in order to develop a core outcome set for use in future meningioma clinical trials., Competing Interests: MDJ received a grant from the National Institute for Health Research Health Technology Assessment program for the Radiation versus Observation for Atypical Meningioma (ROAM) trial (NIHR ID: 12/173/14). MDJ and SJM received a grant from the National Institute for Health Research Health Technology Assessment program for Surgeons Trial Of Prophylaxis for Epilepsy in seizure naïve patients with Meningioma (STOP’EM; NIHR ID: NIHR129748). TS founded and leads the Anaplastic Meningioma International Consortium (AMiCo). TS and MDJ co-founded the British-Irish Meningioma Society (BIMS). AGM is a National Institute for Health Research (NIHR) Senior Investigator and is also part-funded by NIHR ARC North West Coast. The views expressed in this article are those of the author(s) and not necessarily those of the NIHR, or the Department of Health and Social Care. MP has received honoraria for lectures, consultation or advisory board participation from the following for-profit companies: Bayer, Bristol-Myers Squibb, Novartis, Gerson Lehrman Group (GLG), CMC Contrast, GlaxoSmithKline, Mundipharma, Roche, BMJ Journals, MedMedia, Astra Zeneca, AbbVie, Lilly, Medahead, Daiichi Sankyo, Sanofi, Merck Sharp & Dome, Tocagen, Adastra, Servier. MW has received research grants from Quercis and Versameb, and honoraria for lectures or advisory board participation or consulting from Bayer, Curevac, Medac, Novartis, Novocure, Orbus, Philogen, Roche, and Sandoz., (© The Author(s) 2024. Published by Oxford University Press, the Society for Neuro-Oncology and the European Association of Neuro-Oncology.)

Background: Intracranial meningioma with bone involvement and primary intraosseous meningioma is uncommon. There is currently no consensus for optimal management. This study aimed to describe the management strategy and outcomes for a 10-year illustrative cohort, and propose an algorithm to aid clinicians in selecting cranioplasty material in such patients., Methods: A single-centre, retrospective cohort study (January 2010-August 2021). All adult patients requiring cranial reconstruction due to meningioma with bone involvement or primary intraosseous meningioma were included. Baseline patient and meningioma characteristics, surgical strategy, and surgical morbidity were examined. Descriptive statistics were performed using SPSS v24.0. Data visualisation was performed using R v4.1.0., Results: Thirty-three patients were identified (mean age 56 years; SD 15) There were 19 females. Twenty-nine patients had secondary bone involvement (88%). Four had primary intraosseous meningioma (12%). Nineteen had gross total resection (GTR; 58%). Thirty had primary 'on-table' cranioplasty (91%). Cranioplasty materials included pre-fabricated polymethyl methacrylate (pPMMA) (n = 12; 36%), titanium mesh (n = 10; 30%), hand-moulded polymethyl methacrylate cement (hPMMA) (n = 4; 12%), pre-fabricated titanium plate (n = 4; 12%), hydroxyapatite (n = 2; 6%), and a single case combining titanium mesh with hPMMA cement (n = 1; 3%). Five patients required reoperation for a postoperative complication (15%)., Conclusion: Meningioma with bone involvement and primary intraosseous meningioma often requires cranial reconstruction, but this may not be evident prior to surgical resection. Our experience demonstrates that a wide variety of materials have been used successfully, but that pre-fabricated materials may be associated with fewer postoperative complications. Further research within this population is warranted to identify the most appropriate operative strategy., (© 2023. The Author(s).)

Purpose: For patients with a new lesion on CT head (CTH) suspected to be a brain tumor, a staging chest, abdomen, and pelvis CT (CTCAP) is only warranted if a metastatic lesion is suspected. Unnecessary CTCAPs are often performed too early in a patient's journey due to poor patient selection. We sought to create a protocol to guide the selection of patients for CTCAPs based on their CTH findings., Methods: Patients with suspected new brain tumors discussed at the neuro-oncology MDT at a tertiary neurosurgical center were reviewed. Patient demographics and CTH features were collected. For protocol creation, data was collected from July to December 2020, and predictor variables were identified using multivariate logistic regression. Candidate protocols were assessed in a protocol testing stage using similar data collected from January to June 2021. Sensitivity, specificity, and area under the curve (AUC) were computed for each protocol., Results: Variables from the protocol creation stage (222 patients) were assessed in the protocol testing stage (216 patients). The most sensitive variables predicting metastatic disease were a previous history of cancer, multiple lesions, lesion < 4 cm, and infratentorial location. A protocol recommending a CTCAP based on the presence of one of these features has a sensitivity of 99.1% (AUC 0.704)., Conclusions: Unnecessary CTCAPs are reduced if performed only if a patient has one of the four identified predictor variables., (© 2022. Crown.)

Background: After meningioma surgery, approximately 1 in 3 patients will have residual tumor that requires ongoing imaging surveillance. The precise volumetric growth rates of these tumors are unknown., Objective: To identify the volumetric growth rates of residual meningioma, growth trajectory, and factors associated with progression., Methods: Patients with residual meningioma identified at a tertiary neurosurgery center between 2004 and 2020 were retrospectively reviewed. Tumor volume was measured using manual segmentation, after surgery and at every follow-up MRI scan. Growth rates were ascertained using a linear mixed-effects model and nonlinear regression analysis of growth trajectories. Progression was defined according to the Response Assessment in Neuro-Oncology (RANO) criteria (40% volume increase)., Results: There were 236 patients with residual meningioma. One hundred and thirty-two patients (56.0%) progressed according to the RANO criteria, with 86 patients being conservatively managed (65.2%) after progression. Thirteen patients (5.5%) developed clinical progression. Over a median follow-up of 5.3 years (interquartile range, 3.5-8.6 years), the absolute growth rate was 0.11 cm 3 per year and the relative growth rate 4.3% per year. Factors associated with residual meningioma progression in multivariable Cox regression analysis were skull base location (hazard ratio [HR] 1.60, 95% CI 1.02-2.50) and increasing Ki-67 index (HR 3.43, 95% CI 1.19-9.90). Most meningioma exhibited exponential and logistic growth patterns (median R 2 value 0.84, 95% CI 0.60-0.90)., Conclusion: Absolute and relative growth rates of residual meningioma are low, but most meet the RANO criteria for progression. Location and Ki-67 index can be used to stratify adjuvant treatment and surveillance paradigms., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Congress of Neurological Surgeons.)

Tranexamic Acid (TXA) has been used in medical and surgical practice to reduce haemorrhage. The aim of this review was to evaluate the effect of TXA use on intraoperative and postoperative outcomes of meningioma surgery. A systematic review and meta-analysis was conducted in accordance with the PRISMA statement and registered in PROSPERO (CRD42021292157). Six databases were searched up to November 2021 for phase 2-4 control trials or cohort studies, in the English language, examining TXA use during meningioma surgery. Studies ran outside of dedicated neurosurgical departments or centres were excluded. Risk of bias was assessed using the Cochrane Risk of Bias 2 tool. Random effects meta-analysis were performed to delineate differences in operative and postoperative outcomes. Four studies (281 patients) were included. TXA use significantly reduced intraoperative blood loss (mean difference 315.7 mls [95% confidence interval [CI] -532.8, -98.5]). Factors not affected by TXA use were transfusion requirement (odds ratio = 0.52; 95% CI 0.27, 0.98), operation time (mean difference = -0.2 h; 95% CI -0.8, 0.4), postoperative seizures (Odds Ratio [OR] = 0.88; 95% CI 0.31, 2.53), hospital stay (mean difference = -1.2; 95% CI -3.4, 0.9) and disability after surgery (OR = 0.50; 95% CI 0.23, 1.06). The key limitations of this review were the small sample size, limited data for secondary outcomes and a lack of standardised method for measuring blood loss. TXA use reduces blood loss in meningioma surgery, but not transfusion requirement or postoperative complications. Larger trials are required to investigate the impact of TXA on patient-reported postoperative outcomes., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Introduction: Few studies have evaluated meningioma patients' longer-term health-related quality of life (HRQoL) following diagnosis and treatment, particularly in those with incidental, actively monitored tumours., Methods: A single-center, cross-sectional study was completed. Adult patients with surgically managed or actively monitored meningioma with more than five years of follow-up were included. The patient-reported outcome measures RAND SF-36, EORTC QLQ-C30 and QLQ-BN20 were used to evaluate HRQoL. HRQoL scores were compared to normative population data. Outcome determinants were evaluated using multivariate linear regression analysis., Results: 243 patient responses were analyzed, and the mean time from diagnosis was 9.8 years (range 5.0-40.3 years). Clinically relevant, statistically significant HRQoL impairments were identified across several SF-36 and QLQ-C30 domains. Increasing education level (β = 2.9, 95% CI 0.9 to 4.9), P = .004), employment (β = 7.7, 95% CI 2.2 to 13.1, P = .006) and absence of postoperative complications (β=-6.7, 95% CI -13.2 to (-)0.3, P = .041) were associated with a better QLQ-C30 summary score. Other tumour and treatment variables were not., Conclusion: This study highlights the longer-term disease burden of patients with meningioma nearly one decade after diagnosis or surgery. Patients with actively monitored meningioma have similar HRQoL to operated meningioma patients. Healthcare professionals should be mindful of HRQoL impairments and direct patients to sources of support as needed., (© 2022. The Author(s).)

Background: Sporadic multiple meningioma are uncommon. Population-based data suggests that these patients have a reduced overall survival when compared to patients with solitary meningioma. The aim of this study was to investigate the clinical outcomes in multiple and solitary meningioma., Methods: A single-center matched cohort study (2008-2018) was performed. Patients with synchronous multiple meningioma at presentation, with no history of prior intracranial radiation, concurrent hormone replacement therapy or features of NF2-schwannomatosis were included. Eligible patients were matched 1:1 to patients with solitary meningioma. Outcomes of interest were occurrence of an intervention, recurrence, new meningioma development and mortality., Results: Thirty-four patients harboring 76 meningioma at presentation were included. Mean age was 59.3 years (SD = 13.5). Thirty-one (91.2%) were female. The median number of meningioma per patient was 2 (range 2-6). Eighteen patients (52.9%) were symptomatic at presentation. Median overall follow-up was 80.6 months (IQR 44.1-99.6). Compared to patients with a sporadic meningioma, there was no difference in intervention rates (67.6% vs 70.6%, P = 0.792). Eight patients (34.8%) with a multiple meningioma had a WHO grade 2 meningioma compared to 7 (29.2%) with a solitary meningioma (P = 0.679). Median recurrence-free survival was 89 months (95% CI 76-104) with no difference between the two groups (P = 0.209). Mean overall survival was 132 months (95% CI 127-138) with no difference between the two groups (P = 0.860). One patient with multiple meningioma developed two further new meningioma 36 months following diagnosis., Conclusion: Sporadic multiple meningioma may not have worse clinical outcomes. Management of patients with sporadic multiple meningioma should be tailored towards the symptomatic meningioma or high-risk asymptomatic meningioma., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Tumour Treating Fields (TTF) in combination with standard therapy, prolongs survival in patients with glioblastoma (GBM). The aim of the current study was to assess the feasibility of integrating TTF into a standard UK neuro-oncology service with a focus on patient tolerability, compliance, and treatment delivery., Methods: A prospective study was performed of UK patients with IDH 1 Wild Type, MGMT Unmethylated GBM treated with TTF, in conjunction with conventional therapy. Patient compliance data, device-specific tolerability questions, and an evaluation of disease progression and survival were collected. Monthly quality of life (QoL) questionnaires (EORTC QLQ-C30 with BN-20) examined the trend of global health, psychosocial function, and symptom progression., Results: Nine patients were enrolled with a median age of 47 (seven males; two females). Overall, compliance with TTF was 89% (range 16-97%). Only one patient failed to comply with treatment. Patients tolerated the device with minimal side effects. Eight patients described mild to moderate skin irritation, whilst all patients were keen to recommend the device to other patients (100%). Most patients found the weight and size of the device to be its biggest drawback (72%). Progression-free survival was 5.5 months and median overall survival was 14.9 months., Conclusions: TTF was well-tolerated amongst a small cohort of UK patients, who were able to comply with treatment without any significant complication. QoL questionnaires showed no sustained deterioration in global health, physical and emotional function until the final months of life when the disease burden was greatest.

Core Outcome Sets (COS) define minimum outcomes to be measured and reported in clinical effectiveness trials for a particular health condition/health area. Despite recognition as critical to clinical research design for other health areas, none have been developed for neuro-oncology. COS development projects should carefully consider: scope (how the COS should be used), stakeholders involved in development (including patients as both research partners and participants), and consensus methodologies used (typically a Delphi survey and consensus meeting), as well as dissemination plans. Developing COS for neuro-oncology is potentially challenging due to extensive tumor subclassification (including molecular stratification), different symptoms related to anatomical tumor location, and variation in treatment options. Development of a COS specific to tumor subtype, in a specific location, for a particular intervention may be too narrow and would be unlikely to be used. Equally, a COS that is applicable across a wider area of neuro-oncology may be too broad and therefore lack specificity. This review describes why and how a COS may be developed, and discusses challenges for their development, specific to neuro-oncology. The COS under development are briefly described, including: adult glioma, incidental/untreated meningioma, meningioma requiring intervention, and adverse events from surgical intervention for pediatric brain tumors., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Society for Neuro-Oncology.)

Objective: Cranioplasty remains an essential procedure following craniectomy but is associated with high morbidity. We investigated factors associated with outcomes following first alloplastic cranioplasty., Methods: A single-centre, retrospective cohort study of patients undergoing first alloplastic cranioplasty at a tertiary neuroscience centre (01 March 2010-01 September 2021). Patient demographics and craniectomy/cranioplasty details were extracted. Primary outcome was all-cause explantation. Secondary outcomes were explantation secondary to infection, surgical morbidity and mortality. Multivariable analysis was performed using Cox proportional hazards regression or binary logistic regression., Results: Included were 287 patients with a mean age of 42.9 years [SD = 15.4] at time of cranioplasty. The most common indication for craniectomy was traumatic brain injury (32.1%, n = 92). Cranioplasty materials included titanium plate (23.3%, n = 67), hydroxyapatite (22.3%, n = 64), acrylic (20.6%, n = 59), titanium mesh (19.2%, n = 55), hand-moulded PMMA cement (9.1%, n = 26) and PEEK (5.6%, n = 16). Median follow-up time after cranioplasty was 86.5 months (IQR 44.6-111.3). All-cause explantation was 12.2% (n = 35). Eighty-three patients (28.9%) had surgical morbidity. In multivariable analysis, the risk of all-cause explantation and explantation due to infection was reduced with the use of both hydroxyapatite (HR 0.22 [95% CI 0.07-0.71], p  = .011, HR 0.22 [95% CI 0.05-0.93], p  = .040) and acrylic (HR 0.20 [95% CI 0.06-0.73], p  = .015, HR 0.24 [95% CI 0.06-0.97], p  = .045), respectively. In addition, risk of explantation due to infection was increased when time to cranioplasty was between three and six months (HR 6.38 [95% CI 1.35-30.19], p  = .020). Mean age at cranioplasty (HR 1.47 [95% CI 1.03-2.11], p  = .034), titanium mesh (HR 5.36 [95% CI 1.88-15.24], p  = .002), and use of a drain (HR 3.37 [95% CI 1.51-7.51], p  = .003) increased risk of mortality., Conclusions: Morbidity is high following cranioplasty, with over a tenth requiring explantation. Hydroxyapatite and acrylic were associated with reduced risk of all-cause explantation and explantation due to infection. Cranioplasty insertion at three to six months was associated with increased risk of explantation due to infection.

Introduction: Meningioma is the most common primary intracranial tumour in adults. The majority are non-malignant, but a proportion behave more aggressively. Incidental/minimally symptomatic meningioma are often managed by serial imaging. Symptomatic meningioma, those that threaten neurovascular structures, or demonstrate radiological growth, are usually resected as first-line management strategy. For patients in poor clinical condition, or with inoperable, residual or recurrent disease, radiotherapy is often used as primary or adjuvant treatment. Effective pharmacotherapy treatments do not currently exist. There is heterogeneity in the outcomes measured and reported in meningioma clinical studies. Two 'Core Outcome Sets' (COS) will be developed: (COSMIC: Intervention) for use in meningioma clinical effectiveness trials and (COSMIC: Observation) for use in clinical studies of incidental/untreated meningioma., Methods and Analysis: Two systematic literature reviews and trial registry searches will identify outcomes measured and reported in published and ongoing (1) meningioma clinical effectiveness trials, and (2) clinical studies of incidental/untreated meningioma. Outcomes include those that are clinician reported, patient reported, caregiver reported and based on objective tests (eg, neurocognitive tests), as well as measures of progression and survival. Outcomes will be deduplicated and categorised to generate two long lists. The two long lists will be prioritised through two, two-round, international, modified eDelphi surveys including patients with meningioma, healthcare professionals, researchers and those in caring/supporting roles. The two final COS will be ratified through two 1-day online consensus meetings, with representation from all stakeholder groups., Ethics and Dissemination: Institutional review board (University of Liverpool) approval was obtained for the conduct of this study. Participant eConsent will be obtained prior to participation in the eDelphi surveys and consensus meetings. The two systematic literature reviews and two final COS will be published and freely available., Trial Registration Number: COMET study ID 1508., Competing Interests: Competing interests: MDJ received a grant from the National Institute for Health Research Health Technology Assessment programme for the Radiation versus Observation for Atypical Meningioma (ROAM) trial (NIHR ID: 12/173/14). MDJ received a grant from the National Institute for Health Research Health Technology Assessment programme for Surgeons Trial Of Prophylaxis for Epilepsy in seizure-naïve patients with Meningioma (STOP'EM) (NIHR ID: NIHR129748). TS founded and leads the Anaplastic Meningioma International Consortium (AMICo). TS and MDJ co-founded the British-Irish Meningioma Society (BIMS). MP has received honoraria for lectures, consultation or advisory board participation from the following for-profit companies: Bayer, Bristol Myers Squibb, Novartis, Gerson Lehrman Group (GLG), CMC Contrast, GlaxoSmithKline, Mundipharma, Roche, BMJ Journals, MedMedia, AstraZeneca, AbbVie, Lilly, Medahead, Daiichi Sankyo, Sanofi, Merck Sharp & Dohme, Tocagen, Adastra. The following for-profit companies have supported clinical trials and contracted research conducted by MP with payments made to his institution: Boehringer Ingelheim, Bristol Myers Squibb, Roche, Daiichi Sankyo, Merck Sharp & Dohme, Novocure, GlaxoSmithKline, AbbVie. MW has received research grants from Apogenix, Merck Sharp & Dohme, Merck (EMD) and Quercis, and honoraria for lectures or advisory board participation or consulting from Adastra, Bristol Myers Squibb, Medac, Merck Sharp & Dohme, Merck (EMD), Nerviano Medical Sciences, Novartis, Orbus, Philogen and yMabs., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Brain metastases comprise 40% of all metastatic tumours and breast tumours are among the tumours that most commonly metastasise to the brain, the role that epigenetic gene dysregulation plays in this process is not well understood. We carried out 450 K methylation array analysis to investigate epigenetically dysregulated genes in breast to brain metastases (BBM) compared to normal breast tissues (BN) and primary breast tumours (BP). For this, we referenced 450 K methylation data for BBM tumours prepared in our laboratory with BN and BP from The Cancer Genome Atlas. Experimental validation on our initially identified genes, in an independent cohort of BP and in BBM and their originating primary breast tumours using Combined Bisulphite and Restriction Analysis (CoBRA) and Methylation Specific PCR identified three genes (RP11-713P17.4, MIR124-2, NUS1P3) that are hypermethylated and three genes (MIR3193, CTD-2023M8.1 and MTND6P4) that are hypomethylated in breast to brain metastases. In addition, methylation differences in candidate genes between BBM tumours and originating primary tumours shows dysregulation of DNA methylation occurs either at an early stage of tumour evolution (in the primary tumour) or at a later evolutionary stage (where the epigenetic change is only observed in the brain metastasis). Epigentic changes identified could also be found when analysing tumour free circulating DNA (tfcDNA) in patient's serum taken during BBM biopsies. Epigenetic dysregulation of RP11-713P17.4, MIR3193, MTND6P4 are early events suggesting a potential use for these genes as prognostic markers., (© 2022. The Author(s).)

Introduction: Due to the increased use of CT and MRI, the prevalence of incidental findings on brain scans is increasing. Meningioma, the most common primary brain tumour, is a frequently encountered incidental finding, with an estimated prevalence of 3/1000. The management of incidental meningioma varies widely with active clinical-radiological monitoring being the most accepted method by clinicians. Duration of monitoring and time intervals for assessment, however, are not well defined. To this end, we have recently developed a statistical model of progression risk based on single-centre retrospective data. The model Incidental Meningioma: Prognostic Analysis Using Patient Comorbidity and MRI Tests (IMPACT) employs baseline clinical and imaging features to categorise the patient with an incidental meningioma into one of three risk groups: low, medium and high risk with a proposed active monitoring strategy based on the risk and temporal trajectory of progression, accounting for actuarial life expectancy. The primary aim of this study is to assess the external validity of this model., Methods and Analysis: IMPACT is a retrospective multicentre study which will aim to include 1500 patients with an incidental intracranial meningioma, powered to detect a 10% progression risk. Adult patients ≥16 years diagnosed with an incidental meningioma between 1 January 2009 and 31 December 2010 will be included. Clinical and radiological data will be collected longitudinally until the patient reaches one of the study endpoints: intervention (surgery, stereotactic radiosurgery or fractionated radiotherapy), mortality or last date of follow-up. Data will be uploaded to an online Research Electronic Data Capture database with no unique identifiers. External validity of IMPACT will be tested using established statistical methods., Ethics and Dissemination: Local institutional approval at each participating centre will be required. Results of the study will be reported through peer-reviewed articles and conferences and disseminated to participating centres, patients and the public using social media., Competing Interests: Competing interests: AII is supported by Health Education England (North West) Academic Foundation Programme. CPM is a PhD candidate funded by The Brain Tumour Charity to complete The COSMIC project. DMF is funded by a National Institute for Health Research Academic Clinical Fellowship and Cancer Research UK Predoctoral Bursary. TS founded and leads the Anaplastic Meningioma International Consortium (AMiCo). TS and MDJ cofounded the British-Irish Meningioma Society (BIMS). MDJ received a grant from the National Institute for Health Research Health Technology Assessment programme for the Radiation vs Observation for Atypical Meningioma (ROAM) trial (NIHR ID: 12/173/14). MDJ and SJM received a grant from the National Institute for Health Research Health Technology Assessment programme for Surgeons Trial Of Prophylaxis for Epilepsy in seizure naïve patients with Meningioma (STOP'EM) (NIHR ID: NIHR129748)., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.)

The outcomes following re-operation for meningioma are poorly described. The aim of this study was to identify risk factors for a performance status outcome following a second operation for a recurrent meningioma. A retrospective, comparative cohort study was conducted. The primary outcome measure was World Health Organization performance. Secondary outcomes were complications, and overall and progression free survival (OS and PFS respectively). Baseline clinical characteristics, tumor details, and operation details were collected. Multivariable binary logistic regression was used to identify risk factors for performance status outcome following a second operation. Between 1988 and 2018, 712 patients had surgery for intracranial meningiomas, 56 (7.9%) of which underwent a second operation for recurrence. Fifteen patients (26.8%) had worsened performance status after the second operation compared to three (5.4%) after the primary procedure ( p = 0.002). An increased number of post-operative complications following the second operation was associated with a poorer performance status following that procedure (odds ratio 2.2 [95% CI 1.1-4.6]). The second operation complication rates were higher than after the first surgery (46.4%, n = 26 versus 32.1%, n = 18, p = 0.069). The median OS was 312.0 months (95% CI 257.8-366.2). The median PFS following the first operation was 35.0 months (95% CI 28.9-41.1). Following the second operation, the median PFS was 68.0 months (95% CI 49.1-86.9). The patients undergoing a second operation for meningioma had higher rates of post-operative complications, which is associated with poorer clinical outcomes. The decisions surrounding second operations must be balanced against the surgical risks and should take patient goals into consideration.

Surgical resection of meningioma leaves residual solid tumour in over 25% of patients. Selection for further treatment and follow-up strategy may benefit from knowledge of volumetric growth and factors associated with re-growth. The aim of this review was to evaluate volumetric growth and variables associated with growth in patients that underwent incomplete resection of a meningioma without the use of adjuvant radiotherapy. A systematic review was conducted in accordance with the PRISMA statement and registered a priori with PROSPERO (registration number: CRD42020177052). Six databases were searched up to May 2020. Full text articles analysing volumetric growth rates in at least 10 patients who had residual meningioma after surgery were assessed. Four single-centre, retrospective studies totalling 238 patients were included, of which 99% of meningioma were WHO grade 1. The absolute tumour growth rate ranged from 0.09 to 4.94 cm 3 per year. The relative growth rate ranged from 5.11 to 14.18% per year. Varying methods of volumetric assessment and definitions of growth impeded pooled analysis. Pre-operative and residual tumour volume, and hyperintensity on T2 weighted MRI were identified as variables associated with residual meningioma growth, however this was inconsistent across studies. Risk of bias was high in all studies. Radiological regrowth occurred in 42-67% of cases. Our review identified that volumetric growth of residual meningioma is scarcely reported. Sufficiently powered studies are required to delineate volumetric growth and prognostic factors to stratify management., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Introduction: Radiation induced meningioma (RIM) incidence is increasing in line with improved childhood cancer survival. No optimal management strategy consensus exists. This study aimed to delineate meningioma growth rates from tumor discovery and correlate with clinical outcomes., Methods: Retrospective study of patients with a RIM, managed at a specialist tertiary neuroscience center (2007-2019). Tumor volume was measured from diagnosis and at subsequent interval scans. Meningioma growth rate was determined using a linear mixed-effects model. Clinical outcomes were correlated with growth rates accounting for imaging and clinical prognostic factors., Results: Fifty-four patients (110 meningiomas) were included. Median duration of follow-up was 74 months (interquartile range [IQR], 41-102 months). Mean radiation dose was 41 Gy (standard deviation [SD] = 14.9) with a latency period of 34.4 years (SD = 13.7). Median absolute growth rate was 0.62 cm 3 /year and the median relative growth rate was 72%/year. Forty meningiomas (between 27 patients) underwent surgical intervention after a median follow-up duration of 4 months (IQR 2-35). Operated RIMs were clinically aggressive, likely to be WHO grade 2 at first resection (43.6%) and to progress after surgery (41%). Median time to progression was 28 months (IQR 13-60.5). A larger meningioma at discovery was associated with growth (HR 1.2 [95% CI 1.0-1.5], P = 0.039) but not progression after surgery (HR 2.2 [95% CI 0.7-6.6], P = 0.181). Twenty-seven (50%) patients had multiple meningiomas by the end of the study., Conclusion: RIMs exhibit high absolute and relative growth rates after discovery. Surgery is recommended for symptomatic or rapidly growing meningiomas only. Recurrence risk after surgery is high.

The unanticipated diagnosis of sporadic Creutzfeldt-Jakob disease (sCJD) in a patient after previous neurosurgery can lead to difficult decisions regarding informing contacts. A patient developed sCJD 3 years after neurosurgery. There were 29 potential contacts and 26 were contacted. Twelve completed a questionnaire. The majority of patients wished to know about the contact and to be seen face-to-face, and their main concern was developing the disease despite verbal and written reassurance that this was unlikely. Informing patients of sCJD contact is difficult and can lead to significant patient anxiety. Face-to-face meetings, a helpline and follow-up can help., (Copyright © 2020 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.)

Background: Incidental findings such as meningioma are becoming increasingly prevalent. There is no consensus on the optimal management of these patients. The aim of this study was to examine the outcomes of patients diagnosed with an incidental meningioma who were treated with surgery or radiotherapy., Methods: Single-center retrospective cohort study of adult patients diagnosed with an incidental intracranial meningioma (2007-2015). Outcomes recorded were postintervention morbidity, histopathologic diagnosis, and treatment response., Results: Out of 441 patients, 44 underwent treatment. Median age at intervention was 56.1 years (interquartile range [IQR], 49.6-66.5); patients included 35 women and 9 men. The main indication for imaging was headache (25.9%). Median meningioma volume was 4.55 cm 3 (IQR, 1.91-8.61), and the commonest location was convexity (47.7%). Six patients underwent surgery at initial diagnosis. Thirty-eight had intervention (34 with surgery and 4 with radiotherapy) after a median active monitoring duration of 24 months (IQR, 11.8-42.0). Indications for treatment were radiologic progression (n = 26), symptom development (n = 6), and patient preference (n = 12). Pathology revealed World Health Organization (WHO) grade 1 meningioma in 36 patients and WHO grade 2 in 4 patients. The risk of postoperative surgical and medical morbidity requiring treatment was 25%. Early and late moderate adverse events limiting activities of daily living occurred in 28.6% of patients treated with radiotherapy. Recurrence rate after surgery was 2.5%. All meningiomas regressed or remained radiologically stable after radiotherapy., Conclusions: The morbidity after treatment of incidental intracranial meningioma is not negligible. Considering most operated tumors are WHO grade 1, treatment should be reserved for those manifesting symptoms or demonstrating substantial growth on radiologic surveillance., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Asymptomatic meningioma is a common incidental finding with no consensus on the optimal management strategy. We aimed to develop a prognostic model to guide personalized monitoring of incidental meningioma patients., Methods: A prognostic model of disease progression was developed in a retrospective cohort (2007-2015), defined as: symptom development, meningioma-specific mortality, meningioma growth or loss of window of curability. Secondary endpoints included non-meningioma-specific mortality and intervention., Results: Included were 441 patients (459 meningiomas). Over a median of 55 months (interquartile range, 37-80), 44 patients had meningioma progression and 57 died (non-meningioma-specific). Forty-four had intervention (at presentation, n = 6; progression, n = 20; nonprogression, n = 18). Model parameters were based on statistical and clinical considerations and included: increasing meningioma volume (hazard ratio [HR] 2.17; 95% CI: 1.53-3.09), meningioma hyperintensity (HR 10.6; 95% CI: 5.39-21.0), peritumoral signal change (HR 1.58; 95% CI: 0.65-3.85), and proximity to critical neurovascular structures (HR 1.38; 95% CI: 0.74-2.56). Patients were stratified based on these imaging parameters into low-, medium- and high-risk groups and 5-year disease progression rates were 3%, 28%, and 75%, respectively. After 5 years of follow-up, the risk of disease progression plateaued in all groups. Patients with an age-adjusted Charlson comorbidity index ≥6 (eg, an 80-year-old with chronic kidney disease) were 15 times more likely to die of other causes than to receive intervention at 5 years following diagnosis, regardless of risk group., Conclusions: The model shows that there is little benefit to rigorous monitoring in low-risk and older patients with comorbidities. Risk-stratified follow-up has the potential to reduce patient anxiety and associated health care costs., (© The Author(s) 2019. Published by Oxford University Press on behalf of the Society for Neuro-Oncology.)

The evolutionary processes that drive universal therapeutic resistance in adult patients with diffuse glioma remain unclear 1,2 . Here we analysed temporally separated DNA-sequencing data and matched clinical annotation from 222 adult patients with glioma. By analysing mutations and copy numbers across the three major subtypes of diffuse glioma, we found that driver genes detected at the initial stage of disease were retained at recurrence, whereas there was little evidence of recurrence-specific gene alterations. Treatment with alkylating agents resulted in a hypermutator phenotype at different rates across the glioma subtypes, and hypermutation was not associated with differences in overall survival. Acquired aneuploidy was frequently detected in recurrent gliomas and was characterized by IDH mutation but without co-deletion of chromosome arms 1p/19q, and further converged with acquired alterations in the cell cycle and poor outcomes. The clonal architecture of each tumour remained similar over time, but the presence of subclonal selection was associated with decreased survival. Finally, there were no differences in the levels of immunoediting between initial and recurrent gliomas. Collectively, our results suggest that the strongest selective pressures occur during early glioma development and that current therapies shape this evolution in a largely stochastic manner.

Purpose: Meningiomas are the commonest predominantly non-malignant brain tumour in adults. The use of surgery appears to be increasing, and outcomes are thought to be good, but whole nation data for England is scarce. The aim of this report is to examine the epidemiology of patients operated for cranial and spinal meningioma in England, and to assess associations between outcomes and gender, age, meningioma site (cranial or spinal), and grade. Material and methods: A search strategy encompassing all patients coded with cranial and spinal meningioma treated between January 1999 and December 2013 was obtained from data linkage between the National Cancer Registration and Analysis Service and Hospital Episode Statistics for England. Results: 25,694 patients were diagnosed with meningioma in England between 1999 and 2013, in whom 24,302 were cranial and 1392 spinal. Of these patients, 14,229 (60%) cranial and 1188 (85%) spinal meningioma received surgery. Of those operated on 70.1% were women, and, where the tumour grade was recorded, 79.5% were WHO grade I, 18.4% grade II, and 2.1% grade III. Five and ten year net survival rates for surgically treated cranial meningiomas were respectively 90% and 81% for those with WHO grade I, 80% and 63% for grade II, and 30% and 15% for WHO grade III tumours. Overall survival after surgery is better in women, younger adults, and people with spinal or lower grade meningiomas. Outcomes have improved over the time period examined. Conclusion: The outcome for patients with meningioma is good and is improving. However, there remains a significant mortality related to the disease process.

Object: Pilocytic astrocytomas are rare tumours in adults. Presentation, management and prognostic factors are poorly characterised. Methods: Retrospective single centre study from 2000 to 2016. Results: 50 cases were identified (median age 29 years; range 16-76). Symptoms at presentation were neurological deficit ( n  = 21), headache ( n  = 18) and seizures ( n  = 6). Five were incidental findings. Five patients had hydrocephalus at presentation and required emergent management, two by endoscopic third ventriculostomy and three by external ventricular drain. Symptoms were present for a median of 16 weeks (range 1 week to 34 years). Surgery consisted of gross total resection ( n  = 23), subtotal resection ( n  = 21) or biopsy ( n  = 6). Progression occurred in 20 patients at a median time of 7 years following surgery and was asymptomatic in just over half of these cases. A greater degree of resection (complete vs. subtotal) was associated with longer time to progression (Kaplan-Meier analysis, log rank test = 3.58, p  = 0.059). At their first progression 12 patients underwent re-resective surgery and the remainder received radiotherapy. The median 5-year survival was 80%. Conclusions: In adult patients with a pilocytic astrocytoma, a macroscopic resection should be the aim at the first resective operation. Emergency management of hydrocephalus may be required in the first instance.

Background: Incidental discovery accounts for 30% of newly-diagnosed intracranial meningiomas. There is no consensus on their optimal management. This review aimed to evaluate the outcomes of different management strategies for these tumors., Methods: Using established systematic review methods, six databases were scanned up to September 2017. Pooled event proportions were estimated using a random effects model. Meta-regression of prognostic factors was performed using individual patient data., Results: Twenty studies (2130 patients) were included. Initial management strategies at diagnosis were: surgery (27.3%), stereotactic radiosurgery (22.0%) and active monitoring (50.7%) with a weighted mean follow-up of 49.5 months (SD = 29.3). The definition of meningioma growth and monitoring regimens varied widely impeding relevant meta-analysis. The pooled risk of symptom development in patients actively monitored was 8.1% (95% CI 2.7-16.1). Associated factors were peritumoral edema (OR 8.72 [95% CI 0.35-14.90]) and meningioma diameter ≥ 3 cm (OR 34.90 [95% CI 5.17-160.40]). The pooled proportion of intervention after a duration of active monitoring was 24.8% (95% CI 7.5-48.0). Weighted mean time-to-intervention was 24.8 months (SD = 18.2). The pooled risks of morbidity following surgery and radiosurgery, accounting for cross-over, were 11.8% (95% CI 3.7-23.5) and 32.0% (95% CI 10.6-70.5) respectively. The pooled proportion of operated meningioma being WHO grade I was 94.0% (95% CI 88.2-97.9)., Conclusion: The management of incidental meningioma varies widely. Most patients who clinically or radiologically progressed did so within 5 years of diagnosis. Intervention at diagnosis may lead to unnecessary overtreatment. Prospective data is needed to develop a risk calculator to better inform management strategies.

Background: Epilepsy is a major cause of morbidity and mortality in meningioma patients. The aims of this study were to determine which factors predispose meningioma patients to developing perioperative seizures and to understand the impact of antiepileptic drugs., Methods: Patients treated for a histologically-confirmed intracranial meningioma at the authors' institution between 2010 and 2015 were retrospectively examined. Clinical and imaging data were assessed. Multivariate analysis was performed using binary logistic regression. The effect of antiepileptic treatment was assessed using survival analysis., Results: Two hundred and eighty-three patients met the selection criteria; seizures were present in 68 preoperatively (24%) and in 48 patients (17%) following surgery. Of the 68 with preoperative seizures, 19 continued to have them, whereas de-novo seizures arose postoperatively in 29 seizure-naïve patients. Risk factors of postoperative seizures were convexity location (OR 2.05 [95% CI 1.07-3.98], p = 0.030), fronto-parietal location (OR 4.42 [95% CI 1.49-13.16], p = 0.007) and preoperative seizures (OR 2.65 [95% CI 1.37-5.24], p = 0.005). The two locations, in addition to the presence of midline shift on preoperative imaging (OR 4.15 [95% CI 1.54-11.24], p = 0.005), were significantly correlated with postoperative seizures in seizure-naïve patients. Antiepileptic treatment in patients with those risk factors reduced the possibility of seizures at any time point within the 1st year postoperatively by approximately 40%, although this did not meet statistical significance., Conclusion: Prophylactic antiepileptic treatment might be warranted in seizure-naïve meningioma patients with ≥ 1 risk factor. High-quality randomised controlled trials are required to verify those factors and to define the role of antiepileptics in meningioma practice.

Background: Intracranial subependymomas account for 0.2-0.7% of central nervous system tumours and are classified as World Health Organization (WHO) grade 1 tumours. They are typically located within the ventricular system and are detected incidentally or with symptoms of hydrocephalus. Due to paucity of studies exploring this tumour type, the objective was to determine the medium- to long-term outcome of intracranial subependymoma treated by surgical resection., Methods: Retrospective case note review of adults with intracranial WHO grade 1 subependymoma diagnosed between 1990 and 2015 at the Walton Centre NHS Foundation Trust was undertaken. Tumour location, extent of resection (defined as gross total resection (GTR), sub-total resection (STR) or biopsy) and the WHO performance status at presentation and through follow-up were recorded., Results: Thirteen patients (7 males; 6 females) with a mean age of 47.6 years (range 33-58 years) and a median follow-up of 46 months (range 25-220 months) were studied. Eight patients had symptomatic tumours (headache, visual disturbance); five had incidental finding. Tumours were most commonly located in the fourth ventricle (n = 8). The performance status scores at diagnosis were 0 (n = 8) and 1 (n = 5). The early post-operative performance status scores at 6 months were 0 (n = 5) and 1 (n = 8) and at last follow-up were 0 (n = 11) and 1 (n = 2). There was no evidence of tumour re-growth following GTR or STR. The commonest complication was hydrocephalus (n = 3)., Conclusion: Subependymoma are indolent tumours. No patients exhibited a worsening of performance status at medium- to long-term follow-up and there were no tumour recurrence suggesting a shorter follow-up time may be sufficient. Surgical resection is indicated for symptomatic tumours or those without a clear imaging diagnosis. Incidental intraventricular subependymoma can be managed conservatively through MRI surveillance.

Background: Increasingly, biomarkers have been identified that correlate with improved overall and progression-free survival (OS and PFS) in glioblastoma, including MGMT methylation status and mutations in the IDH1 gene. In this study, we investigated the clinical and biological factors associated with long-term survival in glioblastoma patients treated with chemoradiotherapy., Method: Demographic and clinical data were collected for all patients with glioblastoma diagnosed between May 2004 and September 2007, treated with chemoradiotherapy and with associated tissue samples available for biomarker analysis. MGMT methylation was determined by pyrosequencing. IDH1 mutation was identified by R132H immunohistochemistry. Univariate Cox regression analysis of factors associated with survival and Kaplan-Meier survival analysis was performed using the SPSS statistics package., Results: One hundred patients were included in the study. Median follow-up was 12.2 months (range 1.6-102.4). Median OS was 12.1 months (95 % CI: 10.8-13.3) and median PFS was 8.2 months (95 % CI: 6.8-9.5). The 2-, 3- and 5-year survival was 18, 9 and 6 % respectively. Three patients are still alive at 7.4, 8.3 and 8.5 years after diagnosis. Cox proportional-hazards regression identified independent prognostic factors for OS, female (p = 0.019), MGMT methylation (p < 0.0001) and IDH1 mutation (p = 0.023), and for PFS, MGMT methylation (p = 0.001) and IDH1 mutation (p = 0.018). Kaplan-Meier survival analysis showed that MGMT(methylated)/IDH1(+ve) was associated with a significantly longer OS 66.8 months (95 % CI: 0.0-167.8) and PFS 16.9 months (95 % CI: 11.1-22.7) when compared with MGMT(methylated)/IDH1(-ve) OS 15.5 months (95 % CI: 11.6-19.4) and PFS 9.4 months (95 % CI: 8-10.8) (log-rank, P = 0.000) and MGMT(unmethylated)/IDH1(-ve) OS 11.1 months (95 % CI: 8.5-13.7) and PFS 6.3 months (95 % CI: 4.4-8.3) (log-rank, p = 0.000)., Conclusions: While the importance of MGMT methylation is well established, we demonstrate that the combination of MGMT(methylated)/IDH1(+ve) is associated with considerably longer OS and PFS in this series of chemoradiotherapy-treated glioblastoma tumours. The long-term cognitive function and quality of life in these long-term survivors warrant investigation.

Objective: To examine whether Simpson grade and pathology location are still predictors of recurrence/progression free survival (RPFS) in WHO grade 1 cranial meningiomas., Methods: A retrospective case series of all WHO grade 1 cranial meningiomas undergoing surgical resection at our institution between 2002 to 2007 was performed. Demographic and outcome data included: Simpson grade, extent of resection [gross total (Simpson 1-3) and sub total (Simpson 4-5)], tumour location, timing of post-operative imaging and outpatient review, time to recurrence and subsequent management. Statistical analysis was by Kaplan-Meier survival curves., Results: 145 cases were included of which 75% were female, with an overall median age of 55 years. 24% had parasagittal, 23% convexity and 53% skull base meningioma. 21% had a grade 1 Simpson resection, 43% grade 2, 35% grade 4 and 1% grade 5. The median follow up period was 60 months with a median 5.5 outpatient appointments and 5 post-operative imaging studies. 10 cases (6.9%) had recurrence/progression at a median period of 42 months. Of these, 4 remained under active surveillance, 3 received stereotactic radiosurgery and 3 were treated with fractionated radiotherapy. 5 year recurrence/progression free survival (RPFS) for Simpson grade 1 was 96.8%, 2: 100%, 4: 82.4% and 5: 0%. Simpson grade (p=0.01) and gross total/sub total resection (p=0.001) were significant predictors of RPFS. Meningioma location was not a significant predictor of RPFS (p-value 0.836)., Conclusion: Simpson grade remains a significant predictor of RPFS in WHO grade 1 meningioma surgery. However, tumour location was not significant in this series. We advocate different post-operative imaging surveillance protocols depending on gross total or sub total surgical resection., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Background: World Health Organization grade II astrocytomas (AII) are the commonest low-grade glioma subset, but their prognostic factors are subject to debate. This institutional study aimed to identify prognostic factors in lobar AII., Methods: Retrospective review of newly diagnosed, lobar AII between 2006 and 2012. Patient demographics, imaging, and treatment data were obtained. Isocitrate dehydrogenase-1 (IDH1) status was assessed via immunohistochemistry. Multivariate analysis was performed with Cox regression to identify prognostic factors for overall survival (OS) and progression-free survival (PFS)., Results: A total of 92 adult patients were identified with a median age of 42 years (range 20-73 years) and median follow-up period of 45 months (range, 7-98 months). Seizures were the commonest mode of presentation (75%). IDH1 immunopositivity was seen in 46 of 83 patients (55%). Radiology diagnosis agreed with histology in 76% of cases, and 28% of tumors had documented evidence of some degree of contrast enhancement. Surgical management was either resection (51%) or biopsy (49%) and postoperative radiotherapy was used in patients with unfavorable prognostic features. The median OS and PFS were 85 months (range 2-98 months) and 36 months (95% confidence interval [95% CI] 27-45 months), respectively. Surgical resection (P < 0.001; hazard ratio [HR] 5.072; 95% CI 2.050-12.550), absence of contrast enhancement (P = 0.006; HR 3.180; 95% CI 1.403-7.206), and IDH1 immunopositivity (P = 0.006; HR 3.310; 95% CI 1.416-7.738) were associated with improved OS. Good performance status (P = 0.005; HR 5.965; 95% CI 1.710-20.804) and absence of contrast enhancement (P < 0.001; HR 3.446; 95% CI 1.883-6.304) were associated with improved PFS., Conclusions: Patients with World Health Organization grade II astrocytomas have better overall survival if their tumor is nonenhancing, amenable to surgical resection, and exhibits the IDH1 mutation. These factors should be used to guide patient management and inform prognosis., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: Tumour metastasis to the brain is a common and deadly development in certain cancers; 18-30 % of breast tumours metastasise to the brain. The contribution that gene silencing through epigenetic mechanisms plays in these metastatic tumours is not well understood., Results: We have carried out a bioinformatic screen of genome-wide breast tumour methylation data available at The Cancer Genome Atlas (TCGA) and a broad literature review to identify candidate genes that may contribute to breast to brain metastasis (BBM). This analysis identified 82 candidates. We investigated the methylation status of these genes using Combined Bisulfite and Restriction Analysis (CoBRA) and identified 21 genes frequently methylated in BBM. We have identified three genes, GALNT9, CCDC8 and BNC1, that were frequently methylated (55, 73 and 71 %, respectively) and silenced in BBM and infrequently methylated in primary breast tumours. CCDC8 was commonly methylated in brain metastases and their associated primary tumours whereas GALNT9 and BNC1 were methylated and silenced only in brain metastases, but not in the associated primary breast tumours from individual patients. This suggests differing roles for these genes in the evolution of metastatic tumours; CCDC8 methylation occurs at an early stage of metastatic evolution whereas methylation of GANLT9 and BNC1 occurs at a later stage of tumour evolution. Knockdown of these genes by RNAi resulted in a significant increase in the migratory and invasive potential of breast cancer cell lines., Conclusions: These findings indicate that GALNT9 (an initiator of O-glycosylation), CCDC8 (a regulator of microtubule dynamics) and BNC1 (a transcription factor with a broad range of targets) may play a role in the progression of primary breast tumours to brain metastases. These genes may be useful as prognostic markers and their products may provide novel therapeutic targets.

Introduction: Low-grade gliomas (LGGs) are slow-growing and diffusely infiltrating tumours constituting 25-30 % of adult gliomas. Rarely, these tumours may arise in the cerebral midline, including the thalamus, hypothalamus, tectum and brainstem. Here we present a contemporary experience with midline LGGs., Methods: Midline LGGs were identified from a retrospective database of adult patients who received a histological diagnosis of WHO grade II glioma between 2006 and 2012 at a single institution. Location, radiological data and clinical outcomes were collected. IDH1 status was assessed by immunohistochemistry., Results: Eighteen patients with midline LGGs were identified, with a median age of 45. Most received biopsy upon diagnosis, though asymptomatic patients with tectal tumours underwent active surveillance. Oligodendroglial tumours were much less common than in a comparable group of lobar tumours (6 vs. 38 %, Fisher's exact test, p = 0.007). Only one tumour was immunopositive for IDH1 (1/17). Radiological diagnosis correlated with histology in only 71 % of patients. Median survival of midline LGGs was 48 months (3-90 months) and radiological features such as contrast enhancement, size and radiological diagnosis did not predict survival in this cohort. Median overall survival of midline LGGs was less than lobar LGGs (log-rank, p = 0.006), though differences became insignificant when considering only biopsied astrocytomas in both locations (log-rank, p = 0.491)., Conclusions: Diagnosis of midline LGGs is complicated by both limitations of biopsy and imaging. Midline tumours have a poorer prognosis compared to lobar equivalents and survival differences are probably due to the absence of significant surgical intervention in midline locations.

Fluid transport in syringomyelia has remained enigmatic ever since the disease was first identified some three centuries ago. However, accumulating evidence in the last decade from animal studies implicates arterial pulsations in syrinx formation. In particular, it has been suggested that a phase difference between the pressure pulse in the spinal subarachnoid space and the perivascular spaces, due to a pathologically disturbed cerebrospinal fluid (CSF) or blood supply, could result in a net influx of CSF into the spinal cord (SC). A lumped-parameter model is developed of the cerebrospinal system to investigate this conjecture. It is found that although this phase-lag mechanism may operate, it requires the SC to have an intrinsic storage capacity due to the collapsibility of the contained venous reservoir. This net flux is associated with a higher mean pressure in the SC than the SSS which is maintained in the periodic steady state. According to our simulations the mechanical perturbations of arachnoiditis exacerbate the phase-lag effect, which may be partially alleviated by the presence of a posttraumatic syrinx and more completely by a syringo-subarachnoid shunt., (Copyright © 2010 IPEM. Published by Elsevier Ltd. All rights reserved.)

The discovery of a genetic signature of chemosensitivity and prognosis in oligodendroglial tumours prompted a new optimism in glioma management. After more than a decade since the initial reports, where do we stand in the current management of oligodendroglial tumours? This review focuses on the latest molecular genetics, imaging characteristics, and recent trials of treatment paradigms for these tumours.

Purpose: Apparent diffusion coefficient (ADC) describes water diffusion within tissues. Previous studies report a negative linear correlation between minimum ADC and tumour cellularity in different types of gliomas, but there are no studies in oligodendroglial tumours. This study evaluated the relationship between ADC and tumour cellularity in oligodendroglial tumours characterized by genotype., Methods: ADC was assessed in 17 patients with known 1p/19q status: 3 grade II oligodendrogliomas (OII), 9 grade II oligoastrocytomas (OAII), 5 grade III oligoastrocytomas (OAIII). Regions of interest were placed on ADC maps around tumour margins to generate mean tumour ADC, and over minimum and maximum tumour ADC. Histopathology assessment of tumour cellularity determined minimum, maximum and mean cell density in serial stereotactic biopsies., Results: 1p/19q loss was present in 2/3 OII, 5/9 OAII, 2/5 OAIII. Grade III tumours had higher maximum cell density than grade II tumours (17.2 vs. 10.57%: Mann Whitney U; P = 0.20). Oligoastrocytoma were more likely to have a lower minimum cell density than oligodendrogliomas (Mann Whitney U; P = 0.032). There was no relationship between cell density and genotype. There was no linear correlation between mean ADC and mean cell density (Spearman's rho; r = 0.486: P = 0.438), minimum ADC and maximum cell density (Spearman's rho; r = 0.158: P = 0.660), and maximum ADC and minimum cell density (Spearman's rho; r = 0.039: P = 0.985)., Conclusions: In oligodendroglial tumours there is no relationship between quantitative assessment of cellularity and ADC. This may reflect differences in oligodendroglial tumour biology compared to other gliomas, although the composition of the extracellular matrix may influence ADC more than cellularity.

Syringomyelia is a disease in which fluid-filled cavities, called syrinxes, form in the spinal cord causing progressive loss of sensory and motor functions. Invasive monitoring of pressure waves in the spinal subarachnoid space implicates a hydrodynamic origin. Poor treatment outcomes have led to myriad hypotheses for its pathogenesis, which unfortunately are often based on small numbers of patients due to the relative rarity of the disease. However, only recently have models begun to appear based on the principles of mechanics. One such model is the mathematically rigorous work of Carpenter and colleagues (2003, "Pressure Wave Propagation in Fluid-Filled Co-Axial Elastic Tubes Part 1: Basic Theory," ASME J. Biomech. Eng., 125(6), pp. 852-856; 2003, "Pressure Wave Propagation in Fluid-Filled Co-Axial Elastic Tubes Part 2: Mechanisms for the Pathogenesis of Syringomyelia," ASME J. Biomech. Eng., 125(6), pp. 857-863). They suggested that a pressure wave due to a cough or sneeze could form a shocklike elastic jump, which when incident at a stenosis, such as a hindbrain tonsil, would generate a transient region of high pressure within the spinal cord and lead to fluid accumulation. The salient physiological parameters of this model were reviewed from the literature and the assumptions and predictions re-evaluated from a mechanical standpoint. It was found that, while the spinal geometry does allow for elastic jumps to occur, their effects are likely to be weak and subsumed by the small amount of viscous damping present in the subarachnoid space. Furthermore, the polarity of the pressure differential set up by cough-type impulses opposes the tenets of the elastic-jump hypothesis. The analysis presented here does not support the elastic-jump hypothesis or any theory reliant on cough-based pressure impulses as a mechanism for the pathogenesis of syringomyelia.

This edition of the British Journal of Neurosurgery's picture quiz provides a series of questions to test the practising neurosurgeon and neurosurgeon in training on syringomyelia, Chiari malformations, and the associated anatomy and fluid dynamics.