Predictors of future haemorrhage from cerebral cavernous malformations: a retrospective cohort study.

Cerebral cavernous malformations (CCMs) are commonly diagnosed, with a low reported rate of haemorrhage on long-term follow-up. The identification of factors predictive of future haemorrhage risk would assist in guiding the management of patients with CCM. The aim of this study was to identify variables associated with haemorrhage, and calculate haemorrhage risk in CCM. We conducted a retrospective study of patients diagnosed with a CCM, managed at a specialist tertiary neuroscience centre (2007-2019). The primary outcome was symptomatic haemorrhage, and secondary outcomes were variables associated with increased risk of haemorrhage, using multivariable Cox regression analysis. Included were 545 patients, with 734 confirmed cavernomas. Median age at diagnosis was 47 (interquartile range [IQR] 35-60), with a median follow-up duration after diagnosis of 46 months (IQR 19-85). Of the patients, 15.0% had multiple lesions (N = 82/545). Symptomatic presentation was observed in 52.5% of patients (N = 286/545). The annual haemorrhage rate was 1.00% per lesion-year (25 events in 2512 lesion-years), and higher in those with symptoms at presentation (1.50% per lesion-year, 22 events vs 0.29%, 3 events, P < 0.001). The variables associated with symptomatic haemorrhage were increased size (hazard ratio [HR] 1.04, 95% confidence interval [CI] 1.01-1.07, P = 0.004), eloquent location (HR 2.63, 95% CI 1.12-6.16, P = 0.026), and symptomatic haemorrhage at presentation (HR 5.37, 95% CI 2.40-11.99, P < 0.001). This study demonstrated that CCMs have a low haemorrhage rate. Increased size, eloquent location, and haemorrhage at presentation appear to be predictive of a higher risk of haemorrhage, and could be used to stratify management protocols.

Volumetric Growth and Growth Curve Analysis of Residual Intracranial Meningioma.

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.

Sporadic multiple intracranial meningioma does not infer worse patient outcomes: results from a case control study.

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.

External validation of brain arteriovenous malformation haemorrhage scores, AVICH, ICH and R2eD.

PURPOSE: To externally validate the arteriovenous malformation-related intracerebral haemorrhage (AVICH), intracerebral haemorrhage (ICH), and novel haemorrhage presentation risk score (R2eD) in brain arteriovenous malformations. METHODS: Adult 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. RESULTS: Two 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). CONCLUSIONS: The 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.

Clinical Outcomes Following Re-Operations for Intracranial Meningioma.

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.

Neurosurgery activity levels in the United Kingdom and republic of Ireland during the first wave of the covid-19 pandemic - a retrospective cross-sectional cohort study.

The impact of Covid-19 on surgical patients worldwide has been substantial. In the United Kingdom (UK) and the Republic of Ireland (RoI), the first wave of the pandemic occurred in March 2020. The aims of this study were to: (1) evaluate the volume of neurosurgical operative activity levels, Covid-19 infection rate and mortality rate in April 2020 with a retrospective cross-sectional cohort study conducted across 16 UK and RoI neurosurgical centres, and (2) compare patient outcomes in a single institution in April-June 2020 with a comparative cohort in 2019. Across the UK and RoI, 818 patients were included. There were 594 emergency and 224 elective operations. The incidence rate of Covid-19 infection was 2.6% (21/818). The overall mortality rate in patients with a Covid-19 infection was 28.6% (6/21). In the single centre cohort analysis, an overall reduction in neurosurgical operative activity by 65% was observed between 2020 (n = 304) and 2019 (n = 868). The current and future impact on UK neurosurgical operative activity has implications for service delivery and neurosurgical training.

Volumetric growth of residual meningioma - A systematic review.

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 cm3 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.

The growth rate and clinical outcomes of radiation induced meningioma undergoing treatment or active monitoring.

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 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. 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.