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ABSTRACTObjectiveTo assess the risk of intracranial meningioma associated with the use of selected progestogens.DesignNational case-control study.SettingFrench National Health Data System (ie, Système National des Données de Santé).ParticipantsOf 108 366 women overall, 18 061 women living in France who had intracranial surgery for meningioma between 1 January 2009 and 31 December 2018 (restricted inclusion periods for intrauterine systems) were deemed to be in the case group. Each case was matched to five controls for year of birth and area of residence (90 305 controls).Main outcome measuresSelected progestogens were used: progesterone, hydroxyprogesterone, dydrogesterone, medrogestone, medroxyprogesterone acetate, promegestone, dienogest, and intrauterine levonorgestrel. For each progestogen, use was defined by at least one dispensation within the year before the index date (within three years for 13.5 mg levonorgestrel intrauterine systems and five years for 52 mg). Conditional logistic regression was used to calculate odds ratio for each progestogen meningioma association.ResultsMean age was 57.6 years (standard deviation 12.8). Analyses showed excess risk of meningioma with use of medrogestone (42 exposed cases/18 061 cases (0.2%) v 79 exposed controls/90 305 controls (0.1%), odds ratio 3.49 (95% confidence interval 2.38 to 5.10)), medroxyprogesterone acetate (injectable, 9/18 061 (0.05%) v 11/90 305 (0.01%), 5.55 (2.27 to 13.56)), and promegestone (83/18 061 (0.5%) v 225/90 305 (0.2 %), 2.39 (1.85 to 3.09)). This excess risk was driven by prolonged use (≥one year). Results showed no excess risk of intracranial meningioma for progesterone, dydrogesterone, or levonorgestrel intrauterine systems. No conclusions could be drawn concerning dienogest or hydroxyprogesterone because of the small number of individuals who received these drugs. A highly increased risk of meningioma was observed for cyproterone acetate (891/18 061 (4.9%) v 256/90 305 (0.3%), odds ratio 19.21 (95% confidence interval 16.61 to 22.22)), nomegestrol acetate (925/18 061 (5.1%) v 1121/90 305 (1.2%), 4.93 (4.50 to 5.41)), and chlormadinone acetate (628/18 061 (3.5%) v 946/90 305 (1.0%), 3.87 (3.48 to 4.30)), which were used as positive controls for use.ConclusionsProlonged use of medrogestone, medroxyprogesterone acetate, and promegestone was found to increase the risk of intracranial meningioma. The increased risk associated with the use of injectable medroxyprogesterone acetate, a widely used contraceptive, and the safety of levonorgestrel intrauterine systems are important new findings.

Awake surgery for low-grade gliomas is currently considered the best procedure to improve the extent of resection and guarantee a \"worth living life\" for patients, meaning avoiding not only motor but also cognitive deficits. However, tumors located in the right hemisphere, especially in the right frontal lobe, are still rarely operated on in awake condition; one of the reasons possibly being that there is little information in the literature describing the rates and nature of long-lasting neuropsychological deficits following resection of right frontal glioma. To investigate long-term cognitive deficits after awake surgery in right frontal IDH-mutated glioma. We retrospectively analyzed a consecutive series of awake surgical resections between 2012 and 2020 for right frontal IDH-mutated glioma. We studied the patients' subjective complaints and objective neuropsychological evaluations, both before and after surgery. Our results were then put in perspective with the literature. Twenty surgical cases (including 5 cases of redo surgery) in eighteen patients (medium age: 42.5 [range 26–58]) were included in the study. The median preoperative volume was 37 cc; WHO grading was II, III and IV in 70%, 20%, and 10% of cases, respectively. Preoperatively, few patients had related subjective cognitive or behavioral impairment, while evaluations revealed mild deficits in 45% of cases, most often concerning executive functions, attention, working memory and speed processing. Immediate postoperative evaluations showed severe deficits of executive functions in 75% of cases but also attentional deficits (65%), spatial neglect (60%) and behavioral disturbances (apathy, aprosodia/amimia, emotional sensitivity, anosognosia). Four months after surgery, although psychometric z-scores were unchanged at the group level, individual evaluations showed a slight decrease of performance in 9/20 cases for at least one of the following domains: executive functions, speed processing, attention, semantic cognition, social cognition. Our results are generally consistent with those of the literature, confirming that the right frontal lobe is a highly eloquent area and suggesting the importance of operating these patients in awake conditions.

AbstractObjectiveTo assess the risk of meningioma associated with use of high dose cyproterone acetate, a progestogen indicated for clinical hyperandrogenism.DesignObservational cohort study.SettingData from SNDS, the French administrative healthcare database, between 2007 and 2015.Participants253 777 girls and women aged 7-70 years living in France who started cyproterone acetate between 2007 and 2014. Participants had at least one reimbursement for high dose cyproterone acetate and no history of meningioma or benign brain tumour, or long term disease status. Participants were considered to be exposed when they had received a cumulative dose of at least 3 g during the first six months (139 222 participants) and very slightly exposed (control group) when they had received a cumulative dose of less than 3 g (114 555 participants). 10 876 transgender participants (male to female) were included in an additional analysis.Main outcome measureSurgery (resection or decompression) or radiotherapy for one or more intracranial meningiomas.ResultsOverall, 69 meningiomas in the exposed group (during 289 544 person years of follow-up) and 20 meningiomas in the control group (during 439 949 person years of follow-up) were treated by surgery or radiotherapy. The incidence of meningioma in the two groups was 23.8 and 4.5 per 100 000 person years, respectively (crude relative risk 5.2, 95% confidence interval 3.2 to 8.6; adjusted hazard ratio 6.6, 95% confidence interval 4.0 to 11.1). The adjusted hazard ratio for a cumulative dose of cyproterone acetate of more than 60 g was 21.7 (10.8 to 43.5). After discontinuation of cyproterone acetate for one year, the risk of meningioma in the exposed group was 1.8-fold higher (1.0 to 3.2) than in the control group. In a complementary analysis, 463 women with meningioma were observed among 123 997 already using cyproterone acetate in 2006 (risk of 383 per 100 000 person years in the group with the highest exposure in terms of cumulative dose). Meningiomas located in the anterior skull base and middle skull base, particularly the medial third of the middle skull base, involving the spheno-orbital region, appeared to be specific to cyproterone acetate. An additional analysis of transgender participants showed a high risk of meningioma (three per 14 460 person years; 20.7 per 100 000 person years).ConclusionsA strong dose-effect relation was observed between use of cyproterone acetate and risk of intracranial meningiomas. A noticeable reduction in risk was observed after discontinuation of treatment.

[...]1% of Australian women were concerned by this contraception in 2015, and in the USA, 25.4% of women aged 15–44 years have ever used DMPA in their life (2.6% of American women/year, 1.7 million) (7). [...]a first case-report in 2000 (20), a review of case reports in the USA published in 2023 (21), a large case-control in the USA published in September 2024 (22), and several studies carried out and Indonesia (seven studies, including only three medline-indexed), in which one quarter of women taking contraception use DMPA, have assessed a risk between this contraceptive exposure and intracranial meningiomas (6, 23–29). Interestingly, five non-operated patients showed clear signs of tumour shrinkage after stopping DMPA injections. [...]recently, using US private insurance data, a large case-control study showed that DMPA exposure was associated with meningioma [480 cases of cerebral meningioma exposed to DMPA, OR: 1.68 (95% CI: 1.50–1.87)] (22). [...]two case-controls studies assessed the dose-response association between meningioma risk and DMPA use. [...]Dewata et al. found a specific risk of meningioma among women exposed to DMPA (155 DMPA users/212 cases) of 3.13 (CI: 95%; 2.03–4.85) with a dose-cumulative effect: the longer the duration of exposure to DMPA, the higher the risk for meningioma [duration of 10 to 15 years: OR 2.33 (CI: 95%; 1.31–4.15), and more than 15 years: OR 4.45 (CI: 95%; 2.35–8.35)] (23).

AbstractObjectiveTo assess the risk of intracranial meningioma associated with oral contraceptives containing desogestrel, levonorgestrel, or levonorgestrel combined with oestrogen.DesignCase-control study.SettingFrench national health data system (Système National des Données de Santé).Participants8391 women living in France who required surgery for intracranial meningioma in 2020-23. Each patient was matched to 10 women without intracranial meningioma (controls) on year of birth and area of residence.Main outcome measureRisk of intracranial meningioma associated with oral contraceptives containing desogestrel 75µg, levonorgestrel 30µg, or levonorgestrel 50-150 µg combined with oestrogen, and duration of use: short term use was defined by one or more dispensations within the year before the index date only, and prolonged use was defined by continuous use of one year or more (up to seven or more years of continuous use). Conditional logistic regression was used to calculate odds ratios.Results92 301 women, mean age 59.7 years (standard deviation 12.9 years), were included. Among 8391women who had undergone surgery for intracranial meningioma, 287 (3.4%) used desogestrel 75µg (v 2769/83 910 (3.3%) controls), 17 (0.2%) used levonorgestrel 30 µg (v 140 (0.2%)), and 157 (1.9%) used levonorgestrel combined with oestrogen (v 1933 (2.3%)). In analyses of desogestrel according to duration of use, the odds ratio for risk of intracranial meningioma for short term use was 1.02 (95% confidence interval 0.77 to 1.34) and for prolonged use was 1.32 (1.14 to 1.53). Risk was driven by more than five continuous years of use: odds ratio 1.51 (1.17 to 1.94) for five to seven years and 2.09 (1.51 to 2.90) for ≥7 years. Excess risk was greater in women with meningiomas located in the middle or anterior part of the skull base (1.90 (1.47 to 2.46) and 1.50 (1.17 to 1.93), respectively) and in those who had previously used a progestogen of known associated increased risk (3.30 (2.64 to 4.11)). Results showed no excess risk of intracranial meningioma for levonorgestrel (alone or combined with oestrogen) regardless of duration of use. The estimated number needed to harm with desogestrel was 67 300 women for one intracranial meningioma requiring surgery. Risk was no longer observed one year after discontinuation of desogestrel.ConclusionsThe results showed a small increased risk of intracranial meningioma in women who had used desogestrel 75 µg for more than five continuous years, but no risk in users of levonorgestrel (alone or combined with oestrogen).

BackgroundThe combined transpetrosal approach (CTPA) is a versatile technique suitable for challenging skull base pathologies. Despite the advantages provided by a wide surgical exposure, the soft tissue trauma, complex and time-consuming bony work, and cosmetic issues make it far from patient expectations. In this study, the authors describe a less invasive modification of the CTPA, the mini-combined transpetrosal approach (mini-CTPA), and perform a quantitative comparison between these two approaches.MethodsFive human specimens were used for this study. CTPA was performed on one side and mini-CTPA on the opposite side. The surgical freedom, petroclival and brainstem area of exposure, and maneuverability for 6 anatomical targets, provided by the CTPA and mini-CTPA, were calculated and statistically compared. The bony volumes corresponding to each anterior petrosectomy were also measured and compared. Three clinical cases with an operative video are also reported to illustrate the effectiveness of the approach.ResultsThe question-mark skin incision done along the muscle attachments permits an optimal cosmetic result. Even though the limited incision, the smaller craniotomy, and the less extensive bone drilling of mini-CTPA provide a smaller area of surgical freedom, the areas of exposure of petroclival region and brainstem were not statistically different between the two approaches. The antero-posterior maneuverability for the oculomotor foramen (OF), Meckel’s cave (MC) and the REZ of trigeminal nerve, and the supero-inferior maneuverability for OF, MC, Dorello’s canal, and REZ of CN VII are significantly reduced by the smaller opening. The bony volume of anterior petrosectomy resulted similar among the approaches.ConclusionsThe mini-CTPA is an interesting alternative to the CTPA, providing comparable surgical exposure both for petroclival region and for brainstem. Although the lesser soft tissue dissection and bony opening decrease the surgical maneuverability, the mini-CTPA may reduce surgical time, potential approach-related morbidities, and improve cosmetic and functional outcomes for the patients.

BackgroundThe optimal management of tuberculum sellae (TS) meningiomas, especially the surgical strategy, continues to be debated along with several controversies that persist.MethodsA task force was created by the EANS skull base section committee along with its members and other renowned experts in the field to generate recommendations for the surgical management of these tumors on a European perspective. To achieve this, the task force also reviewed in detail the literature in this field and had formal discussions within the group.ResultsThe constituted task force dealt with the practice patterns that exist with respect to pre-operative radiological investigations, ophthalmological and endocrinological assessments, optimal surgical strategies, and follow-up management.ConclusionThis article represents the consensually derived opinion of the task force with respect to the surgical treatment of tuberculum sellae meningiomas. Areas of uncertainty where further clinical research is required were identified.

Purpose The main objective was to assess the neuropsychological, epileptical, and oncological outcomes in a series of patients operated on for a IDH-mutated diffuse low-grade glioma (DLGG) of incidental discovery (iDLGG). Methods We retrospectively reviewed a consecutive series of surgically treated adults with DLGG and selected cases incidentally discovered. Tumor volumes, growth rates, and extents of resection (EOR) were assessed by volumetric measures of fluid-attenuated inversion recovery magnetic resonance imaging. The data on oncological, functional, and epileptical results were retrieved from the patients’ digital files. Results Among all patients with DLGG resected at our center between June 2011 and April 2022, we found eleven cases with an incidental discovery. Resection was supratotal, gross total, and subtotal in 45.5%, 26.4%, and 18.1% of cases, respectively. The rate of epileptic seizures after the surgery was 9.1%. There were 45.4% of patients that had tumor progressions and the overall mean time to tumor progression was 42 months. After the surgery, 3 (27.3%) patients had mild neurocognitive deteriorations, which impeded the return to work in one patient (9.1%). There were no differences with previous series regarding clinical, radiological, and molecular characteristics. Similar results were also found for functional, surgical, epileptical, and oncological outcomes. Conclusion Although the right approach for iDLGG is still a matter of debate, our data support the safety and effectiveness of early surgical resection. More studies are needed to firmly ground this early “preventive” surgery approach.

Skull base chondrosarcoma is a rare tumour usually treated by surgery and proton therapy. However, as mortality rate is very low and treatment complications are frequent, a less aggressive therapeutic strategy could be considered. The objective of this study was to compare the results of surgery only vs surgery and adjuvant proton therapy, in terms of survival and treatment adverse effects, based on a retrospective series. Monocentric retrospective study at a tertiary care centre. All patients treated for a skull base grade I and II chondrosarcoma were included. We collected data concerning surgical and proton therapy treatment and up-to-date follow-up, including Common Terminology Criteria for Adverse Events (CTCAE) scores. 47 patients (23M/24F) were operated on between 2002 and 2015; mean age at diagnosis was 47 years-old (10-85). Petroclival and anterior skull base locations were found in 34 and 13 patients, respectively. Gross total resection was achieved in 17 cases (36%) and partial in 30 (64%). Adjuvant proton therapy (mean total dose 70 GyRBE,1.8 GyRBE/day) was administered in 23 cases. Overall mean follow-up was 91 months (7-182). Of the patients treated by surgery only, 8 (34%) experienced residual tumour progression (mean delay 51 months) and 5 received second-line proton therapy. Adjuvant proton therapy was associated with a significantly lower rate of relapse (11%; p = 0.01). There was no significant difference in 10-year disease specific survival between patients initially treated with or without adjuvant proton therapy (100% vs 89.8%, p = 0.14). Difference in high-grade toxicity was not statistically significant between patients in both groups (25% (7) vs 11% (5), p = 0.10). The most frequent adverse effect of proton therapy was sensorineural hearing loss (39%). Long-term disease specific survival was not significantly lower in patients without adjuvant proton therapy, but they experienced less adverse effects. We believe a surgery only strategy could be discussed, delaying as much as possible proton therapy in cases of relapse. Further prospective studies are needed to validate this more conservative strategy in skull base chondrosarcoma.

BackgroundSurgical treatment of lesions involving the ventral craniovertebral junction (CVJ) and the lower clivus, traditionally involved complex lateral or transoral approaches to the skull base. However, mid or upper clivus involvement requires more extensive lateral approaches. Recently, the endoscopic endonasal approach (EEA) has become the standard for upper CVJ lesions and medial clival, and a valuable alternative for those tumors extending in its upper third as well as laterally. However, the EEA is associated with an increased risk of post-operative CSF leakage and infection when the tumor is characterized by an intradural extension. Furthermore, whenever the tumor has significant lateral and/or inferior extension below the odontoid process, the chances for a complete resection decrease.MethodTo analyze the extent of exposure of a hybrid microscopic-endoscopic transcondylar antero-lateral approach to the CVJ and clival region, and to verify its effectiveness in terms of mid and upper clival access. Five silicone-injected cadaver heads were used. Following a standard antero-lateral approach, condylectomy and jugular tubercle drilling were performed, after which angled endoscopes were utilized to extend the bone resection to the clivus. A volumetric assessment of the amount of clival removal was carried out. A case of CVJ chordoma operated through this approach is presented.ResultsThe hybrid antero-lateral transcondylar approach provides adequate exposure of the ventral CVJ, up to the dorsum sellae and the sphenoid sinus, the contralateral petrous apex, and the contralateral paraclival internal carotid artery (ICA). Approximately 60% of the total clival volume can be removed with this approach. The main limitation is the limited visualization of the ipsilateral paraclival ICA and petrous apex.ConclusionThe hybrid antero-lateral transcondylar approach is a valuable surgical option for CVJ tumor extending from C2 to the mid and upper clivus.