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Aims Signs and symptoms that develop in people with brain tumours are often attributed to their tumour. The prevalence and management of functional neurological symptoms in brain tumour patients have received little attention. This is surprising because functional neurological symptoms complicate management greatly and misdiagnosis can lead to inappropriate treatment and iatrogenic side-effects. Therefore, we investigated the presentation, diagnosis and management of functional neurological disorders (FND) in patients who had a brain or meningeal tumour. Method A retrospective case review was performed from 2017 - 2021 to identify adult brain tumour patients who developed a functional neurological disorder that caused significant disability necessitating expedited investigations. All patients attended a regional neuro-oncology centre. We recorded type of brain tumour and diagnostic investigations. The onset of functional symptoms was divided into three time windows: before tumour diagnosis, after diagnosis and before treatment or after tumour treatment. A neuropsychological review looked for evidence of previous adverse life events. Therapeutic interventions for functional neurological disorder and their outcomes were documented. The case review was combined with a systematic review of the literature to identify the published presentations of functional neurological disorder in the adult brain tumour population. MEDLINE, EMBASE and PsycINFO databases were searched for studies published between January 1980 and February 2021. Results Six patients (5 female, 1 male) were identified from the case review with a median age of 41 (range 29 - 56) years old. Four patients had non-epileptic attack disorder, which was diagnosed with videotelemetry of habitual attacks. One patient had a functional hemiparesis with normal central motor conduction time. One patient had a functional speech disorder with normal EEG. Half of these patients had functional neurological symptoms prior to surgery/oncological treatment. Five patients (83%) were referred for further neuropsychiatric or psychological evaluation. A history of significant psychological trauma prior to the brain tumour diagnosis was elicited in four (66%) patients. Conclusion Patients with either a brain or meningeal tumour may develop functional neurological symptoms. Our findings suggest the possibility that diagnosis of a brain tumour may precipitate a debilitating functional neurological disorder. The neurobiological basis for functional neurological disorders is being actively investigated. There are suggestions in the literature that some brain diseases increase the risk of developing a functional neurological disorder. Further work is needed to determine whether this is true for patients with brain tumours. Increased awareness of functional neurological disorders will improve management. Withdrawal of unnecessary treatment, such as anticonvulsant drugs, reduces the risk of iatrogenic side effects. Initiation of multi-disciplinary care pathways, e.g. physiotherapy, speech and language therapy and psychological treatments, promotes recovery. Collectively, these interventions improve our patients’ quality of life.

Aims Extent of resection is associated with better survival in patients with glioblastoma. Numerous surgical adjuncts can be used to achieve maximal safe resection - including fluorescence-guidance with 5-aminolevulinic acid (5-ALA), neuronavigation, intraoperative ultrasound (IoUS), intra-operative MRI (iMRI), tractography, electrophysiological monitoring and awake surgery. We evaluated the availability, use and operative aim and success associated with these adjuncts. Method This is a prospective cohort study of 27 of 31 neurosurgical centres in the UK and Ireland from 6 January to 19 March 2020. Consecutive cases were identified through neuro-oncology multidisciplinary meetings. Eligible cases included adults with a supratentorial histopathologically confirmed glioblastoma with pre/post-operative reported T1-weighted MRI with contrast deemed suitable for resection. Outcomes included the availability and usage of surgical adjuncts, and the percentage of operations that achieved their aim of complete resection, defined as complete resection of enhancing tumour (CRET) on post-operative T1-MRI. We present the initial descriptive statistics from this national study. Results 232 patients with glioblastoma were included. In 142 patients (61.2%) the surgical aim was CRET. 5-ALA and neuronavigation were available in all centres (Figure 1). The most commonly used neurosurgical adjunct was neuronavigation (88.2%) (Figure 2). The proportion of patients receiving 5-ALA in CRET and debulking-only groups was 65.0% and 48.9%, respectively. 35 different combinations of adjuncts were found in total, with 13 unique combinations only used in one instance (Figures 1 & 2). CRET was achieved in 69/142 (45.8%) patients in which was the aim. 9/90 (10%) patients in the debulking-only group achieved CRET, of which 7/9 (77.8%) had received 5-ALA. Of the three most frequently used combination of adjuncts for patients deemed feasible for CRET, the most successful in terms of achieving CRET was the combined use of neuronavigation, 5-ALA and IoUS, with post-operative CRET at 47.4% (Figure 3). Conclusion ELISAR-GB has collated prospective data to demonstrate the current use of intraoperative adjuncts in the UK and Ireland. There is marked heterogeneity with regards to combinations of adjuncts used. A CRET of 47% is lower than would be expected compared to previously published literature, possibly due to a more stringent definition of complete resection in this study. Based on these early descriptive results, there is no clear combination of adjuncts that shows superiority and use of 5-ALA does not always result in CRET when it is the surgical aim. Of interest, 5-ALA is being used for operations that do not aim for complete resection, a change in indication. The FUTURE GB trial will provide more conclusive evidence on the efficacy of surgical adjuncts to maximise extent of resection.

Surgery for meningiomas involving dural venous sinuses is challenging. We describe a case of a peritorcular meningioma involving major venous sinuses, which was removed using a venous sparing approach with the aid of intraoperative ultrasound. We found ultrasound to be a useful adjunct as it enabled us to get real-time information about the location of venous structures, their function and demonstrate dynamic changes in blood flow during surgery.

Ki67 is a marker for proliferation of a given cell population. Low expression of Ki67 may be associated with a favourable outcome. We investigate how the proliferation index correlates with the location, morphology and behaviour of WHO grade II ependymomas with a single-centre cohort study of adult patients admitted for surgery of WHO grade II ependymomas between 2008 and 2018. Seventeen patients were included, seven had supratentorial and 10 had infratentorial tumours. Three patients died and eight had recurrent disease. Age, gender, location, extent of resection, chemotherapy, radiotherapy and histological markers were not associated with tumour progression. Both unadjusted and adjusted analysis confirmed a higher Ki67 index in male patients. Sensitivity analysis further supported the correlation between Ki67 and male gender. Ki67 may be sex specific but does not seem to correlate with survival and time to recurrence in this series.

In 2016 there were 5250 brain cancer deaths in the UK. Standard treatment is surgical resection followed by chemo-radiotherapy. In most cases of diffuse glioma, complete tumour resection is not feasible. Many chemotherapy drugs have untested penetration through the blood brain barrier, potentially leading to sub-therapeutic concentrations in the tumour. There is need to refine current treatment strategies in relation to the understanding of tumour biology, and rapidly introduce and evaluate novel therapeutic approaches and agents through delivering rigorous clinical trials. The TESSA JOWELL BRAIN MATRIX Study will evaluate the feasibility of delivering precision medicine for brain cancer patients within the NHS. A multicentre, platform feasibility study of 1200 patients with diffuse glioma will build on the 100,000 genome project to develop and evaluate an infrastructure to collect and integrate: 1) real time comprehensive integrated molecular analysis, including whole genome sequencing and epigenetic classification; 2) serial sampling and annotation of tumours; 3) collection of matched clinical data; 4) assessment of patient quality of life; 5) centralised radiological review and response assessment as per RANO criteria. Once developed this will allow rapid introduction of therapeutic trials to specific patient groups. Secondary objectives include: understanding the association between extent of resection and molecular stratification to refine the role of surgery; optimisation and harmonisation of protocols to best collect, manage and store tissue, clinical data, and radiological images in order to provide a resource for researchers, both within and outside of the study. Improve patient recruitment by identifying and removing recruitment barriers and improve the information and consent processes for patients. Promote the development of a national network with expertise in brain cancer. Enrolment of the first patient is expected in late 2019. For further information, please contact the Brain Matrix Trial Office BrainMatrix@trials.bham.ac.uk.

Objectives Paragangliomas are rare neuro-endocrine neoplasms which may occur at multiple anatomical sites, typically the adrenal glands. In the CNS, they can affect the head and neck, and more rarely the lumbar region. Primary lumbar paragangliomas are prominently vascularised lesions which can present variably and pose both diagnostic and surgical challenges. Methods We identified and analysed all cases of lumbar paraganglioma confirmed both surgically and histologically, treated at our regional neurosurgical centre. We collected retrospective clinical, radiological, surgical and histological data. Results We treated 25 patients with confirmed paraganglioma between 1997–2018. This included 19 primary tumours, of which 13 cases of primary lumbar paraganglioma (8 males (61.5%); mean age 51.3 years, range 33.2 – 68.9). Patients presented most frequently with a recent worsening of long-standing lower back pain and sciatica. 7 patients were admitted as emergency cases, including 3 with cauda equina syndrome. The average Ki67 mitotic index was 5.7% (range 1 – 10%). Conclusion We present one of the largest case series of primary lumbar paragangliomas to date to the best of our knowledge. Defining these clinical, radiological, surgical and histological features may be of assistance in recognising and managing this surgical disease.

Background Supratentorial Metastatic Melanomas are common and increasingly treated with immunotherapy. While improving the outcome, the immunotherapy potentially increases the risks of the intracranial surgical procedures, particularly bleeding. However, scarce reports address this complications. Case Description A 52-year old male with a history of right upper limb excised skin lesion resected with wide local excision 6 months prior to admission, who presented with a three weeks history of progressive headaches, vomiting, odd behaviours, forgetfulness, and left lower sided weakness. Brain imaging showed a right frontal lesion with evidence of haemorrhage within it with midline shift and mass effect. He underwent craniotomy and resection of the lesion with no post-operative complication, resolution of left sided hemiparesis and post-operative imaging documenting complete resection and no post-operative complications. The histopathology confirmed metastatic melanoma and he received adjuvant immunotherapy (Nivolumab), however he represented 4 weeks post operatively with sudden onset headache with vomiting with no neurological deficit, brain imaging showed a delayed hematoma in the surgical site. Conclusions This case report highlights the risk of post-operative bleeding with the immunotherapy and paves the way for further studies with regards to the safety of immunotherapy after intracranial procedures

Background Lesions within the corticospinal tract (CST) represent significant surgical challenge with a delicate functional trade-off that should be integrated in the overall patient-centred treatment plan. Methods Patients with lesions within the CST with preoperative cortical and subcortical mapping (nTMS and tractography), intraoperative mapping and intraoperative provisional histological information (smear +- 5-ALA) were included. This independently acquired information was integrated in a decision-making process model to determine the intraoperative extent of resection. Results 10 patients (6 patients with metastatic precentral tumour; 1 patient with Grade III and 2 patients with grade IV gliomas; 1 patient with precentral vascular malformation) were included in the study. Majority of the patient had pre-operative motor deficit (60%). 50% patients underwent gross total resection and 40% patients underwent near total resection of the lesions. In only one patient, no surgical resection was possible after both pre-operative and intraoperative mapping. 70% of patients remained stable postoperatively and 20% improved from previous motor weakness. Conclusion The independently acquired anatomical (anatomical MRI) and functional (nTMS and tractography) in patients with CST lesions provide a more accurate guide for resection. The inclusion of the histological information (smear +- 5-ALA) further allows the surgical team to balance the potential functional risks within the global treatment plan. Therefore, the patient is kept at the centre of the informed decision making process.

Rationale WHO Grade 3 meningiomas are a rare, malignant subtype of meningioma. Few controlled case series detailing its treatment and follow-up are to be found in the literature. Methods Retrospective cohort study of patients treated in a single neuro-oncology centre in the period between September 2008 and March 2019 with an initial diagnosis of WHO Grade 3 meningioma. Demographic and clinical data has been collected from the available medical records. Results 9 patients were included in this series: 2 had convexity, 2 sphenoid wing, 2 parafalcine, 1 parasagittal with a further 3 multiple locations and 1 patient with parietal convexity meningioma. 3 tumours displayed rhabdoid features, whilst 4 displayed papillary features and a further 2 displayed epithelial structures. All patients underwent surgical intervention: 5 patients had a subtotal resection with 3 having total resection. 3/4 of reported Simpson Grading was grade 2, whilst the remaining 1/4 was grade 1. The extent of resection for 1 patient was uncertain. Post surgically, 6 received adjuvant radiotherapy, 2 had no further treatment and 1 received gamma knife therapy. No patient received chemotherapy. 5 patients saw no tumour recurrence at follow up appointments (mean 50 months). Within 2 years of their respective surgical interventions, 4 patients died due to tumour recurrence and associated complications (3 patients). Conclusion To establish a uniform approach to treatment of patients with WHO Grade 3 meningiomas is challenging. Management involves a patient-centred approach based on multidisciplinary meeting decisions. Multicentre registries may allow further conclusions.

Objectives Haemangiopericytoma of the trigemimal nerve is extremely rare, with only two previous cases described to our knowledge. We present the surgical approach to this tumour, and describe a previously poorly reported method of monitoring the function of the branches of the trigeminal nerve: mapping of the sensory roots through transcranial somatosensory cortex sensory evoked potentials (SSEPs), motor evoked potentials (MEP) for the motor root and blink reflex. Design Case and technical reports Subjects 32 year-old male patient presenting with headaches and vomiting, found to have a mixed cystic-solid tumour of the left middle skull base region, in close relation with the foramen ovale and Meckel’s cave. Methods The radiological features of the tumour, technical aspects of the technical approach and neurophysiologic monitoring will be described. Results A pterional craniotomy with fronto-temporal extradural-interdural-intradural approach, and the tumour was debulked with MEP, SSEP and blink reflex monitoring of the branches of the trigeminal nerve. Complete tumour removal was achieved with no post-operative cranial nerve deficits. The histopathology revealed a cystic haemangiopericytoma. Conclusions Haemangiopericytoma is a rare entity. MEP and SSEP monitoring of the trigeminal nerve can be used to achieve complete and safe removal of the tumour.

Merely having the technical ability to perform functional neurosurgery is not sufficient. An understanding of key clinical concepts surrounding movement disorders lies at the heart of becoming a competent functional neurosurgeon in order to ensure correct patient selection and perioperative management. This chapter provides a thorough medical overview of the fundamental clinical aspects, including pathophysiology, diagnosis and medical therapy for the commonest movement disorders encountered in neurosurgical practice: Parkinson’s disease, essential tremor, and dystonia. A brief overview of the surgical management options and outcomes from surgery is discussed. Finally, some of the controversies related to the surgical aspects of movement disorders are examined.

OBJECTIVE: To determine if brain metastasis referrals to the neuro-oncology multidisciplinary team (MDT) in the UK & Ireland comply with current NICE guidelines and to understand how patients are being stratified based on recursive partitioning analysis (RPA) and/or graded prognostic assessment (GPA). METHODS: Prospective multi-centre national audit on all adult patients referred to the local MDT with ≥ 1 cerebral metastasis. After a 2 months trial at King’s College Hospital, neurosurgical units were invited to recruit patients prospectively for a period of 4 months from November 2017. Anonymised data on patient age, type/status of primary malignancy, performance status, location/number of metastases, available imaging, treatment recommendations and length to decision making was entered into a secure online database. Follow-up data will be collected after 12 months. RESULTS: A total of 23/32 units participated. By end of February 2018 data on 579 patients (116% of initial target) had been submitted overall. Preliminary results from King’s College Hospital indicate a mean of 7 [range 3–13] referred cases per MDT. The median age of referred patients was 66 years [range 28–93 years] with 54.1% females and 45.9% males. Solitary metastases only comprised 44.6% of the referrals and specialist intervention (in the form of surgery or stereotactic radiosurgery) was only recommended in 48.0% of cases. The most common primary tumour was lung (33.8%) followed by melanoma (21.0%) and breast (21.0%); other comprised 24.4% (gastrointestinal 10.8%, renal 6.1%, cancer of unknown primary 4.1%, genito-urinary 3.4%). The national results will be presented at the SBNS meeting in autumn 2018. CONCLUSIONS: The preliminary prospective data is in keeping with our previous audit results. This audit will help to draw up a national picture of brain metastases referrals and inform NICE on current work load and MDT management.

Neuro-oncological surgery is a major field of neurosurgery with variety of surgical methods for diagnosis and treatment of different types of brain tumours. Patient reported outcome measures currently in use in neurosurgery do not address the specific needs of the patients with brain tumours. In this study, we identify the unmet needs of brain tumour patients and incorporate them into a framework of specific PROM. A questionnaire survey was conducted among diagnosed cases of brain tumour patients in different stages of treatment during a brain tumour support group meeting. The responses were recorded and analysed and the unmet need of the brain tumour patients were identified. 66.67% of patients mentioned that their physical symptoms were not adequately addressed. Similarly, 33.33% patients felt that their mental and emotional issues were not adequately dealt with during the diagnosis, treatment and follow up period of their brain tumor management. The target population for the PROM will be brain Tumor patients (adult and pediatric). The PROM would collect information from patients preoperatively and Post-operatively. The conceptual domains for neuro-oncology PROM will include health related quality of life (physical, mental, social and emotional), symptoms (specific to neuro-oncology) including weakness, memory, taste, seizure, incontinence, neuro-oncology specific disability and functional status. In conclusion, there is an emergent need to develop a neuro-oncological surgery PROM to address the specific unmet needs of the field of neuro-oncological surgery. The proposed framework would be beneficial in further study and development of the PROM.

BACKGROUND: 5-aminolevulinic acid (5-ALA, Gliolan) use is well documented and established in the resection of adult high-grade gliomas. There is growing interest in its safety and usefulness in the paediatric populations. The main challenge in the latter is the diverse range of histopathological tumour types that can occur. We present the UK’s first case series of 5-ALA use in the paediatric population. METHODS: Parental consent was obtained for the 6 patients (age 1.6–15 years, median 6.5 years) to be given a dose of 20mg/kg of 5-ALA 3 hours pre-operatively. Intra-operatively the tumours were viewed under violet-blue light and the presence of fluorescence was recorded. Fluorescence status was compared with histopathological classification and grade. RESULTS: The case series included: a pilocytic astrocytoma (grade I), a pilomyxoid astrocytoma (II), a glioneuronal tumour (II), a ganglioglioma (II-III), an anaplastic ependymoma (III) and an anaplastic medulloblastoma (IV). Only the grade III ependymoma showed strong fluorescence with 5-ALA. The pilocytic astrocytoma (I) and pilomxyoid astrocytoma (II) showed moderate fluorescence and the ganglioglioma (II-III) showed weak fluorescence. No fluorescence was observed in the glioneuronal tumour (II) or the medulloblastoma (IV). No significant adverse drug reactions were recorded. CONCLUSION: This case series adds to the growing body of evidence demonstrating the safety of 5-ALA in the paediatric population. Our case series highlights the need for larger trials into the usefulness of 5-ALA in the different paediatric brain tumour types. KEYWORDS: 5-aminolevulinic, 5-ALA, Gliolan, Fluoresence, Paediatric, Child, Brain tumour

OBJECTIVE: Tectal plate ‘gliomas’ are uncommon, indolent lesions. Presentation is usually with hydrocephalus and diagnosis is typically made radiologically without histological confirmation. Long term data guiding management is lacking. METHOD: Retrospective review of all paediatric tectal plate lesions in our unit over the last 10 years. RESULTS: Fifteen patients (13 boys, 2 girls; mean age 8.9 years) were identified and included. Most presented with increased intracranial pressure. Fourteen patients (93%) had hydrocephalus at presentation. In 13 patients (87%) there was no progression of the lesion. CSF diversion was performed in 14 patients (93%). The initial intervention was endoscopic third ventriculostomy (ETV) in 12 (80%) and ventriculoperitoneal shunting in 3 (20%). Four patients (33%) were biopsied; 2 (17%) were WHO grade 1 pilocytic astrocytomas and 2 (17%) had non-diagnostic biopsies. Four patients (33%) received adjuvant therapy, two upfront (due to atypical radiological appearances) and 2 due to progression. Of the 4 patients receiving adjuvant therapy, 1 had chemotherapy only (Carboplatin and Vincristine), 1 had chemotherapy followed by proton beam therapy and 2 patients had focal radiation therapy (59.4 CGE). All patients were alive with stable disease at follow up (average 50.5 months; range 0–120 months). CONCLUSION: Our experience is in line with the published literature on the natural history of tectal plate ‘gliomas’ and supports the notion that these are low grade tumours that can be managed with cerebrospinal fluid diversion and surveillance imaging. Adjuvant therapy is reserved for progression and achieves long term control.

BACKGROUND: Autologous dendritic cell immunotherapy has been proven effective in treating tumours outside the central nervous system. Current evidence from phase I and II trials suggest a similar efficacy for central nervous system tumours as well and that an active immune response against these tumours can be generated. OBJECTIVE: We aim to review the literature to identify the types of immune responses against gliomas found to be generated by dendritic cell vaccinations and the types of immune cells subsequently infiltrating the glioma microenvironment. METHODS: A systematic review of the literature was performed by searching the online databases PubMEd, Google Scholar, and EMBASE with use of the keywords intratumoral, infiltration, lymphocytic, vaccination and gliomas. RESULTS: Seven studies reporting lymphocytic infiltration of gliomas microenvironment were identified. Three studies (42.8%) reported presence of tumour infiltrating lymphocytes in 50%, 50% and 28.6% of included patients respectively in the post-vaccination specimens that were not present in the pre-vaccination samples. The remaining 4 (57.2%) reported an up to six-fold increase in the number of pre-existing lymphocytes following vaccination. CONCLUSION: Present data indicate that tumour infiltration by lymphocytes can be induced by dendritic cell immunotherapy and that this may positively affect clinical outcome. It still remains unclear which factors influence the above reaction and therefore prediction of response to treatment is still not possible.

Introduction:The tricyclic antidepressant clomipramine, used clinically since the 1960’s, has been shown to have selective cytotoxicity against glioma cells in vitro and has also been shown to cross the blood brain barrier. While reports suggest clomipramine acts via the mitochondria, the mechanism of action is not fully understood.Materials and Methods:In this study, 8 human biopsy-derived glioblastoma early passage cell lines were treated with 0–200µM clomipramine over 72hrs. Cell viability was measured using the MTS assay, cellular ATP levels using the Cell Titer Glo assay and capsase activation by Caspase-Glo 3/7, 8 and 9 assays. Immunocytochemistry using Mitotracker Red and cytochrome C antibodies was performed. The JC-1 dye was used to evaluate mitochondrial transmembrane potential and DAPI was used to characterise the cell cycle.Results:Clomipramine reduced cell viability in a dose and time dependent manner with IC50 values in the range of 22–60µM at 24hrs. Compared to controls, following 24 hr treatment with 75µM clomipramine, there was a significant reduction of cellular ATP levels (by approximately 100%, p

INTRODUCTION: CD15 and CD15s are cell surface epitopes, known for their ability to bind specific ligands. They are over-expressed on many non-central nervous system (CNS) cancers. Few reports show CD15 expression in CNS neoplasms and in fact, early studies reported the absence of CD15 expression. Recent published reports, however, have identified CD15 as a potential marker for cancer stem-like cells in glioblastomas (GBM). To obtain a better understanding, CD15 and CD15s expression were re-examined in glioma cell lines. METHOD: Extracellular expression of CD15 and CD15s were determined by Immunocytochemistry, Western blotting and flow cytometry in GBM cells (UP-007 and SNB-19). Non-neoplastic astrocytes (SC-1800) served as controls. Cells were synchronised at G1, S or G2/M phases via serum starvation, Hydroxyurea and Colcemid, respectively followed by validation using the fluorescence ubiqutination cell cycle indicator (FUCCI) system. RESULTS: In non-synchronised cultures, only 5-12% of GBM cells expressed CD15 and CD15s where respective cell cycle distributions averaged 55-59% for G1, 6-13% for S and 15-25% for G2/M. When GBM cells were synchronised in G1, a higher percentage of cells expressed CD15 (18-20%) and CD15s (35-50%) compared to SC-1800 cells CD15 (1.5%), CD15s (1.0%). Of GBM cells synchronised in S phase (G1, 25-34%; S, 56-64%; G2/M, 1-5%), 7-10% of GBM cells were CD15 positive. Of GBM cells synchronised to G1/M phase (G1, 20%; S, 6-18%; G2/M, 71-76%) 4.5-14% of cells were CD15 positive. CONCLUSION: CD15 and CD15s expression is cell cycle dependent in glioma cells and may account for the discrepancy of previous experimental data.

INTRODUCTION: Meningiomas are principally benign tumours curable by resection. Many studies have shown a link between Ki-67 labelling indices (LI) and recurrence. Here we seek to improve the grading of meningioma through the use of LI with maximally selected cut points. METHOD: 285 adult meningiomas seen between 1999 and 2004 were examined immunohistochemically using the Ki-67/Mib-1 monoclonal antibody. Statistical analyses, were performed using R-Stats v2.15.1 and the R-Coin package. RESULTS: LI is associated with recurrence free survival (RFS) hazard ratio (HR) (1.09 p = 1.6x10−10). LI is correlated with tumour grade, there were significant differences between the LI means of each WHO grade (I - 4.9%, II - 12.3%, III - 28.7%; p = 2x10−16). Maximal selection of a cut point for RFS using multiple parameters revealed a cut point of LI 10%. Obtaining a further cut point on meningiomas with LI >10% gave the higher cut point of 27%. Kaplan-Meier (KM) analysis of WHO I - III showed a median RFS of 20.28, 8.79, & 1.14 years respectively (p = 3.7x10−8). KM analysis of cut point groups LI 1-10 (LI_A), 11-27 (LI_B), & >27 (LI_C) showed median RFS of 20.28, 7.96, & 1.99 years respectively (p = 6.9x10−13). Cox regression for RFS adjusting for age, gender, WHO grade & LI(A,B,&C) showed that with reference to WHO I, WHO II had a HR of 1.99 p = 0.03, grade III 4.25 p = 0.04; with reference to LI_A, LI_B had a HR of 2.3(1.15 - 4.7) p = 0.02 and LI_C a HR of 10.2(4 - 26) p = 1.2x10−6. CONCLUSION: These results demonstrated stratification, based solely upon the Ki67 labelling index, better predicting recurrence than the current WHO grading. This emphasises the need for LI to be fully incorporated into the grading system of meningiomas.

INTRODUCTION: Pyrosequencing is a method that allows MGMT methylation to be measured in a quantitative manner. MGMT methylation, along with 1p/19q co-deletion and IDH1 mutation, is an important biomarker in high grade gliomas. MGMT methylation indicates an improved response to temozolomide chemotherapy; patients with 1p/19q co-deleted anaplastic oligodendrogliomas benefit from the addition of chemotherapy to radiotherapy. Aim: To compare the average MGMT promoter methylation level of high grade gliomas and correlate it with other clinical parameters and markers including IDH1&2 mutation and 1p/19q co-deletion. METHOD: For 171 high grade gliomas MGMT methylation analysis was performed by pyrosequencing, mutations to IDH1 and IDH2 genes were also detected by pyrosequencing, or immunohistochemistry (n = 166). Screening for 1p/19q deletion was by fluorescence in situ hybridisation (n = 46). Statistical analysis was performed using R-Stats v2.15.2. RESULTS: The results show that higher methylation was correlated with lower grade and mutation to either IDH1 or IDH2 (27.0% vs. 16.6% p = 0.008; and 27.5 vs. 16.1 p = 0.002 respectively). Interestingly 1p/19q co-deletion versus non co-deletion was associated with a particularly high level of methylation (42.2% vs. 17.7% p = 0.001). No significant differences were seen for age or gender. CONCLUSION: The results offer a potential explanation for the improved prognosis seen in glioma patients with 1p/19q co-deletion and when combined with IDH mutation status may provide an extra control to confirm true 1p/19q co-deletion.

Glioblastoma multiforme with an oligodendroglial component (GBMO) has been recognized in the World Health Organization classification-however, the diagnostic criteria, molecular biology, and clinical outcome of primary GBMO remain unclear. Our aim was to investigate whether primary GBMO is a distinct clinicopathological subgroup of GBM and to determine the relative frequency of prognostic markers such as loss of heterozygosity (LOH) on 1p and/or 19q, O(6)-methylguanine-DNA methyltransferase (MGMT) promoter methylation, and isocitrate dehydrogenase 1 (IDH1) mutation.We examined 288 cases of primary GBM and assessed the molecular markers in 57 GBMO and 50 cases of other primary GBM, correlating the data with clinical parameters and outcome.GBMO comprised 21.5% of our GBM specimens and showed significantly longer survival compared with our other GBM (12 mo vs 5.8 mo, P = .006); there was also a strong correlation with younger age at diagnosis (56.4 y vs 60.6 y, P = .005). Singular LOH of 19q (P = .04) conferred a 1.9-fold increased hazard of shorter survival. There was no difference in the frequencies of 1p or 19q deletion, MGMT promoter methylation, or IDH1 mutation (P = .8, P = 1.0, P = 1.0, respectively).Primary GBMO is a subgroup of GBM associated with longer survival and a younger age group but shows no difference in the frequency of LOH of 1p/19q, MGMT, and IDH1 mutation compared with other primary GBM.