Emmanuel Chavredakis

WHO grade 1 meningioma recurrence: Are location and Simpson grade still relevant?

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.

Metastasis-inducing proteins are widely expressed in human brain metastases and associated with intracranial progression and radiation response.

Background:Understanding the factors that drive recurrence and radiosensitivity in brain metastases would improve prediction of outcomes, treatment planning and development of therapeutics. We investigated the expression of known metastasis-inducing proteins in human brain metastases.Methods:Immunohistochemistry on metastases removed at neurosurgery from 138 patients to determine the degree and pattern of expression of the proteins S100A4, S100P, AGR2, osteopontin (OPN) and the DNA repair marker FANCD2. Validation of significant findings in a separate prospective series with the investigation of intra-tumoral heterogeneity using image-guided sampling. Assessment of S100A4 expression in brain metastatic and non-metastatic primary breast carcinomas.Results:There was widespread staining for OPN, S100A4, S100P and AGR2 in human brain metastases. Positive staining for S100A4 was independently associated with a shorter time to intracranial progression after resection in multivariate analysis (hazard ratio for negative over positive staining=0.17, 95% CI: 0.04–0.74, P=0.018). S100A4 was expressed at the leading edge of brain metastases in image guided sampling and overexpressed in brain metastatic vs non-brain metastatic primary breast carcinomas. Staining for OPN was associated with a significant increase in survival time after post-operative whole-brain radiotherapy in retrospective (OPN negative 3.43 months, 95% CI: 1.36–5.51 vs OPN positive, 11.20 months 95% CI: 7.68–14.72, Log rank test, P<0.001) and validation populations.Conclusions:Proteins known to be involved in cellular adhesion and migration in vitro, and metastasis in vivo are significantly expressed in human brain metastases and may be useful biomarkers of intracranial progression and radiosensitivity.

The impact of epilepsy on the quality of life of patients with meningioma: A systematic review

Quality of life (QoL) is regarded as an important outcome measure in meningioma, and studies have investigated the role of various clinical and demographic factors. Epilepsy is known to impair quality of life but the impact of epilepsy on quality of life in a meningioma population is not well defined. The aim of this systematic review is to identify and summarise the current literature on meningioma, epilepsy and quality of life. A PubMed search was performed that identified 162 articles. Only 4 articles relevant to meningioma, epilepsy and QoL were found and each were analysed in terms of design, data, findings and conclusions. Each article was different in terms of study population, aims and outcome measure, but all suggest that epilepsy has an impact on quality of life. Anti-epileptic drugs, uncontrolled seizures and cognitive dysfunction may be particularly significant. The identified articles were weakened by small sample size, short follow-up, a lack of recorded epilepsy variables and the use of quality of life measures that are either too specific or not validated. Future studies are warranted to improve understanding in this topic, aid clinical decisions and improve QoL in these patients.

T cell densities in brain metastases are associated with patient survival times and diffusion tensor MRI changes

Brain metastases are common and are usually detected by MRI. Diffusion tensor imaging (DTI) is a derivative MRI technique that can detect disruption of white matter tracts in the brain. We have matched preoperative DTI with image-guided sampling of the brain-tumor interface in 26 patients during resection of a brain metastasis and assessed mean diffusivity and fractional anisotropy (FA). The tissue samples were analyzed for vascularity, inflammatory cell infiltration, growth pattern, and tumor expression of proteins associated with growth or local invasion such as Ki67, S100A4, and MMP2, 9, and 13. A lower FA in the peritumoral region indicated more white matter tract disruption and independently predicted longer overall survival times (HR for death = 0.21; 95% confidence interval, 0.06-0.82; P = 0.024). Of all the biological markers studied, only increased density of CD3+ lymphocytes in the same region correlated with decreased FA (Mann-Whitney U, P = 0.037) as well as confounding completely the effect of FA on multivariate survival analyses. We conclude that the T-cell response to brain metastases is not a surrogate of local tumor invasion, primary cancer type, or aggressive phenotype and is associated with patient survival time regardless of these biological factors. Furthermore, it can be assayed by DTI, potentially offering a quick, noninvasive, clinically available method to detect an active immune microenvironment and, in principle, to measure susceptibility to immunotherapy.Significance: These findings show that white matter tract integrity is degraded in areas where T-cell infiltration is highest, providing a noninvasive method to identify immunologically active microenvironments in secondary brain tumors. Cancer Res; 78(3); 610-6. ©2017 AACR.

Postoperative seizures in meningioma patients: improving patient selection for antiepileptic drug therapy.

BackgroundEpilepsy 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.MethodsPatients 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.ResultsTwo 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.ConclusionProphylactic 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.

A national survey of the management of patients with incidental meningioma in the United Kingdom

Abstract Background: Incidental meningiomas are increasingly being diagnosed due to widespread use of brain imaging. Treatment options include surveillance, surgery and stereotactic radiosurgery, but the natural history of these tumours is not fully understood and there are no accepted management guidelines to aid clinical decision-making. The aim of this study was to assess current practice in the United Kingdom and identify areas of variation for further study. Methods: A questionnaire was distributed to all members of the Society of British Neurosurgeons (SBNS). The main components of the survey included the assessment of which factors and tumour characteristics are considered in the management and follow-up of incidental meningiomas. Two case scenarios were also presented. Results: The response rate was 12.5% (44 completed surveys) with 74% (25/34) of neurosurgical centres represented. Absence of calcification was only considered by 36% (16/44) of neurosurgeons. Most neurosurgeons opt for surveillance at initial presentation, and the length of follow-up was 5 years (14/33) and 10 years (11/33). The case scenarios highlighted that tumour growth at follow-up resulted in a preference to change from surveillance to treatment with surgery or SRS. SRS was preferred in skull-base (23/36) and medial sphenoid wing (16/39) tumours. Conclusions: This survey has demonstrated that certain aspects of incidental meningioma management show variation and remain controversial. Further research through prospective cohort studies is required to provide evidence to support guidelines for the management of incidental meningiomas.

Cervical vertebral fusion with anterior meningocele.

We present the first described case of cervical vertebral fusion associated with anterior meningocele and syringomyelia. A 45-year-old woman presented with minor trauma, and plain cervical spine radiographs highlighted a congenital deformity of the cervical vertebral bodies. She had a normal neurological examination; however, further imaging revealed a meningocele and syringomyelia. This case highlights the importance of thorough imaging investigation when presented with a congenital deformity in order to detect and prevent development of degenerative spinal cord pathologies.