Background:Meningioangiomatosis is a poorly studied, rare, benign, and epileptogenic brain lesion.

Objective: To demonstrate that surgical resection and a short time interval to surgery improves epileptic seizure control, we performed a systematic review and meta-analysis of meningioangiomatosis cases.

Methods: Using PRISMA-IPD guidelines, the authors performed a systematic review and meta-analysis of histopathologically proven meningioangiomatosis cases.Literature search in the French and English languages (PubMed, Embase, the Cochrane Library and the Science Citation Index) including all studies (January 1981 to June 2020)dealing with histopathologically proven meningioangiomatosis, without age restriction.We assessed clinical, imaging, histomolecular, management, and outcome findings of meningioangiomatosis patients.

Results: Two-hundred and seven cases of meningioangiomatosis from 78 studies were included.The majority of meningioangiomatosis was sporadic, preferentially concerned male patients, younger than 20-year-old, and allowed a functionally independent status. Epileptic seizure was the main symptom, with 81.4%of patients having uncontrolled seizures at the time of surgery. Meningioangiomatosis mainly had frontal (32.3%) or temporal (30.7%) locations. Imaging presentation was heterogeneous, and the diagnosis was often missed pre-operatively. The histopathologic pattern was similar whatever the clinical presentation, and immunohistochemistry had limited diagnostic value. On molecular analysis, allelic loss at 22q12 was more frequent in samples of meningioangiomatosis-associated meningioma (37.5%) than in isolated meningioangiomatosis (23.1%). Time interval from diagnosis to surgery (p=0.011) and lack of surgical resection of the meningioangiomatosis (p=0.009) were independent predictors of post-operative seizure control.

Conclusions: Due to low scientific evidence, a multicentric prospective study should help refining the management of meningioangiomatosis.

Search Methodology

The first author (AR) conducted the literature searchin the US National Library of Medicine (PubMed/MEDLINE), Embase (OVID), the Cochrane Library and the Science Citation Index in June 2020 to identify all reported cases of meningioangiomatosis (from January 1981 to June 2020). The following specific search terms were used: (meningioangiomatosis[All Fields] OR (meningeal[All Fields] AND ("angiomatosis"[MeSH Terms] OR "angiomatosis"[All Fields])) OR meningio-angiomatosis[All Fields] OR meningoangiomatosis[All Fields] OR meningo-angiomatosis[All Fields]). The first author (AR) screened all retrieved titles and abstracts. All full-text publications were reviewed for each potentially eligible study by AR and validated by an external evaluator (JP), which validated the exclusion of studies based on the abstracts.

Selection criteria

Publications were eligible if they met the following criteria: (1) full-text articles written in French and/or English; (2) studies or case reports including at least one case of patient harbouring a histopathologically proven meningioangiomatosis. We performed a systematic review and meta-analysis of histopathologically proven meningioangiomatosis cases. We used the Preferred Reporting Items for Systematic Reviews and Meta-Analyses of Individual Participant Data (PRISMA-IPD) guidelines, as recommended.

Data extraction

For each patient, data of interest were extracted from the original article (AR) and were entered into a dedicated form, which was previously designed and validated by a senior neuropathologist (ELZ), a senior neuroradiologist (CO) and a senior neurosurgeon (JP). The quality of the selected articles was assessed by a dedicated tool, namely the Quality Assessment of Case-Control studies of the National Heart, Lung and Blood institute freely available at https://www.nhlbi.nih.gov/health-topics/study-quality-assessment-tools.

Heterogeneity Testing, Meta-Analysis Model, and Bias Risk Assessment

For dichotomous variable (pre-operative seizure, pre-operative and post-operative seizure control), proportion were calculated for IPD assessment using collated frequencies. The results were than pooled in random effects meta-analyses using Der Simonian and Laird model in order to verify heterogeneity level between the studies and testing the bias risk. The extent of heterogeneity was quantified using the Cochrane Q and the I-squared statistic (which gives the percentage of variation between studies due to heterogeneity rather than chance) and visually through inspection of the forest-plot. All analyses were performed using the Meta XL package (version 5.3, © EpiGear International 2011-2016). The method used to stabilize the variance was the double arcsine transformation.

Quantitative analysis

A descriptive analysis is provided using individual patient data for the demographic parameters, as well as the clinical variables related to the disease. For each demographic and clinical variable with at least 40 valid cases, 1,000 bootstrap evaluation was conducted to build the 95% bootstrap Confidence Interval using the Efron’s BCa method.

Multivariate analyses

Finally, considering pre-operative seizure, pre-operative and post-operative seizure control as the dependent variables, in order to evaluate correlations between the covariates considered and to make adjustments for both socio-demographic factors and the baseline clinical variables, a logistic regression model was used with block entry of variables. To minimize error due to multiplicity of comparisons, only variables associated at the p<0.1 level in unadjusted analysis were processed into multivariate logistic regression models. A p-value of <0.05 was considered statistically significant. Quantitative and multivariate analyses were performed with IBM Corp. Released 2011 IBM SPSS Statistics for Windows (Version 20.0. Armonk, NY: IBM Corp).

Receiver Operating Characteristic curves 

To evaluate the age at surgery and the time interval from diagnosis to surgery as predictors of epileptic seizure at surgery, receiver operating characteristic (ROC) curves were plotted using the presence of epileptic seizures at surgery as a binary outcome across different age thresholds (years) and across different time interval thresholds (months). The analyses were performed using MedCalc Statistical Software (version 19.1.3, MedCalc Software bv, Ostend, Belgium; https://www.medcalc.org; 2019).

Standard Protocol Approvals, Registrations, and Patient Consents

We conducted this study in compliance with the ethical standards of the French legislation.

Data availability

Anonymized data will be shared by request from any qualified investigator.