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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.

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.MethodsRetrospective 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.ResultsFifty-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 cm3/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.ConclusionRIMs 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.

PurposeTo externally validate the arteriovenous malformation-related intracerebral haemorrhage (AVICH), intracerebral haemorrhage (ICH), and novel haemorrhage presentation risk score (R2eD) in brain arteriovenous malformations.MethodsAdult patients diagnosed radiologically with an arteriovenous malformation (AVM) at a tertiary neurosurgical centre between 2007 and 2018 were eligible for inclusion. Both the AVICH and ICH scores were calculated for AVM-related symptomatic haemorrhage (SH) and compared against the modified Rankin scale (mRS) at discharge and last follow-up, with unfavourable outcome defined as mRS > 2. R2eD scores were stratified based on presentation with SH. External validity was assessed using Harrel’s C-statistic.ResultsTwo hundred fifty patients were included. Mean age at diagnosis was 46.2 years [SD = 16.5]). Eighty-seven patients (34.8%) had a SH, with 83 included in the analysis. Unfavourable mRS outcome was seen in 18 (21.6%) patients at discharge and 18 (21.6%) patients at last follow-up. The AVICH score C-statistic was 0.67 (95% confidence interval [CI], 0.53–0.80) at discharge and 0.70 (95% CI, 0.56–0.84) at last follow-up. The ICH score C-statistic was 0.78 (95% CI 0.67–0.88), at discharge and 0.80 (95% CI 0.69–0.91) at last follow-up. The R2eD score C-statistic for predicting AVM haemorrhage was 0.60 (95% CI, 0.53–0.67).ConclusionsThe AVICH score showed fair-poor performance, while the ICH score showed good-fair performance. The R2eD score demonstrated poor performance, and its clinical utility in predicting AVM haemorrhage remains unclear.

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.

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.

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.

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.

To examine whether Simpson grade and pathology location are still predictors of recurrence/progression free survival (RPFS) in WHO grade 1 cranial meningiomas. 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. 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). 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.