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Introduction Usually benign, pituitary tumors (PT) can be invasive and aggressive with a propensity to progress and/or recur. Trouillas's clinicopathological classification attempts to predict the evolutionary risk of a PT. In this study, we assessed the prognostic value of this classification in an independent patient cohort and analyzed its impact on treatment strategies. Patients and methods In this study, 607 patients operated on between 2008 and 2018 for a PT were included. Grading was established based on invasion, proliferative activity (Ki-67, mitotic index) and p53 positivity. The therapeutic management following surgery was analyzed. Progression-free survival (PFS) of the graded tumors was estimated (Kaplan–Meier method and log-rank test) and a multivariate analysis was performed (Cox regression model). Results Grading identified non-invasive PT without (grade 1a: 303 cases) or with proliferative activity (grade 1b: 53 cases) and invasive PT without (grade 2a: 202 cases) or with proliferative activity (grade 2b: 49 cases). The mean follow-up was 47 ± 30 months (median: 38 months). Progression/recurrence occurred in 127 cases. Grades were significant and independent predictors of PFS (P Discussion Grading of a PT according to Trouillas's classification predicts its risk of progression and should advocate for a personalized therapeutic approach in invasive and proliferative tumors. Significance statement This is the first study to assess, on a cohort of 607 well-characterized patients, the real-life therapeutic impact of the five-tiered clinicopathological classification of pituitary tumors. First, we validate that pituitary tumor grades predict the evolutionary risk of the tumor, with a significant higher risk of progression/recurrence in invasive and/or proliferative tumors (mean follow-up: 47 ± 30 months, median: 38 months). Moreover, our study provides evidence that patients with proliferative tumors have a higher risk to be retreated after primary surgery and point toward the fact that radiotherapy can successfully control tumor growth in case of progression or recurrence. Our findings advocate for a personalized therapeutic approach in clinically aggressive pituitary tumors.

68Ga-DOTATOC PET could be a noninvasive, highly sensitive, and specific technique for the challenging diagnosis of optic nerve sheath meningioma (ONSM). Our objective was to report the use and results of 68Ga-DOTATOC PET in suspected ONSM. Twelve subjects who underwent 68Ga-DOTATOC PET for suspected ONSM in our department were retrospectively included. Standardised clinical and radiological data were collected. The PET examination results were classified as positive or negative, and lesion standardised uptake values (SUVmax) were recorded. 68Ga-DOTATOC PET confirmed positive uptake in six cases (SUVmax > 5), leading to ONSM diagnoses followed by radiation therapy in patients with vision loss. Six 68Ga-DOTATOC PET scans were considered negative (SUVmax < 5); these comprised one case of neurosarcoidosis, one cavernous malformation, and four uncertain diagnoses, leading to further investigation. 68Ga-DOTATOC PET was helpful in tumour volume delineation before radiation therapy, leading to a decrease in dose exposure. Noninvasive 68Ga-DOTATOC PET should be performed before treating nonhistologically proven meningiomas with radiotherapy or stereotactic radiosurgery, particularly in cases of uncertain diagnosis with MRI, which characterises most ONSM cases. PET SUVmax thresholds to distinguish meningioma from nonspecific uptake in other lesions need to be adapted to ONSM. 68Ga-DOTATOC PET improves the intraorbital lesion diagnostic approach and therefore impacts therapeutic management.

Background The benefits of decompressive craniectomy (DC) have been demonstrated in malignant ischemic stroke and traumatic brain injuries with refractory intracranial hypertension (ICH) by randomized controlled trials. Some reports advocate the potential of DC in the context of ICH due to meningoencephalitis (ME) with focal cerebral edema but its interest remains controversial especially when there is diffuse cerebral edema. The aim of this study is to assess the benefits of DC in meningoencephalitis with malignant cerebral edema whether it is focal or diffuse. Methods We report two cases successfully treated in our instution, plus we conducted a systematic literature review focused on cases of DC in ME in compliance with prisma guidelines. Results the first patient is a 36-years-old woman who suffered from fulminant pneumococcal meningoencephalitis (ME) with refractory ICH following a transphenoidal removal of pituitary adenoma. The second patient is a 20-years-old man suffering from neuromeningeal cryptococcosis with refractory ICH. In both cases DC led to major clinical improvement with a GOS-E 8 at one year. These results are consistent with the literature review which reports a favorable outcome in 85% of cases. Conclusions DC appears to be a promising therapeutic option in cases of ME with refractory ICH. Thus, reliable criteria will have to be defined to guide us in our practice in emergency cases where DC has not been part of the therapeutic arsenal yet.

PFS6 and PFS12 depending of the in intention-to-treat or per protocole analyses as investigator or central review analyses.

Study of correlation between SSTR2A receptor expression and growth rate (GR) before and under treatment as with progression. No significant correlation was observed. Immunohistochemical detection of SSTR2A protein was performed on 5 µm thick formalin fixed paraffin embedded (FFPE) tissue sections with Ventana Benchmark XT. The monoclonal SSTR2A antibody (clone UMB1, Abcam) was used at 1/4000 dilution.

Purpose:Aggressive meningiomas that progress after surgery/radiotherapy represent an unmet medical need. Strong and constant expression of SSTR2A receptors and activation of the Pi3K/Akt/mTOR pathway have been demonstrated in meningiomas. The combination of everolimus, an mTOR inhibitor, and octreotide, a somatostatin agonist, has shown additive antitumor effect in vitro. The phase II CEVOREM trial investigated the efficacy of this combination on recurrent meningiomas.Patients and Methods:Patients with documented recurrent tumor progression ineligible for further surgery/radiotherapy were eligible to receive octreotide (30 mg/d, day 1) and everolimus (10 mg/d, days 1–28). The primary endpoint was the 6-month progression-free survival rate (PFS6). The secondary endpoints were overall survival, response rate, tumor growth rate according to central review, and safety.Results:A total of 20 patients were enrolled, including 2 with World Health Organization (WHO) grade I tumors, 10 with WHO grade II tumors, and 8 with WHO grade III tumors; furthermore, 4 patients harbored NF2 germline mutation. The overall PFS6 was 55% [95% confidence interval (CI), 31.3%–73.5%], and overall 6- and 12-month survival rates were 90% (95% CI, 65.6%–97.4%) and 75% (95% CI, 50.0%–88.7%), respectively. A major decrease (>50%) was observed in the growth rate at 3 months in 78% of tumors. The median tumor growth rate decreased from 16.6%/3 months before inclusion to 0.02%/3 months at 3 months (P < 0.0002) and 0.48%/3 months at 6 months after treatment (P < 0.0003).Conclusions:The combination of everolimus and octreotide was associated with clinical and radiological activity in aggressive meningiomas and warrants further studies. Decrease in the tumor volume growth rate should be considered a complementary and sensitive endpoint to select potentially effective drugs for recurrent meningiomas.

Supplementary Figure 2 from Somatostatin Receptor sst2 Decreases Cell Viability and Hormonal Hypersecretion and Reverses Octreotide Resistance of Human Pituitary Adenomas

Supplementary Figure Legends 1-2 from Somatostatin Receptor sst2 Decreases Cell Viability and Hormonal Hypersecretion and Reverses Octreotide Resistance of Human Pituitary Adenomas

Supplementary Figure 1 from Somatostatin Receptor sst2 Decreases Cell Viability and Hormonal Hypersecretion and Reverses Octreotide Resistance of Human Pituitary Adenomas

BACKGROUND/OBJECTIVE Aneurysmal subarachnoid hemorrhage (aSAH) is a life-threatening event with major complications such as delayed cerebral ischemia (DCI) or acute hydrocephalus and poor neurological outcome. DCI occurs most frequently 7 days after aSAH and can last for a prolonged period. The ability to predict these complications would allow the neuro-intensivist to identify patients at risk and select the most appropriate unit for hospitalization. To determine the most predictive radiological scales in grading subarachnoid or ventricular hemorrhage or both for functional outcome at 3 months in a large aSAH population, we conducted a single centre retrospective study in a neurocritical care unit. METHODS A 3-year single-centre retrospective cohort study of 230 patients hospitalized for aSAH was analysed. Initial computed tomography (CT) scans in patients hospitalized for aSAH were blindly assessed using eight grading systems: the Fisher grade, modified Fisher grade, Barrow Neurological Institute scale, Hijdra scale, Intraventricular Hemorrhage (IVH) score, Graeb score, and LeRoux score. We evaluated and compared these radiological scales for the early prediction of DCI, acute hydrocephalus, and poor neurological outcome at 3 months. RESULTS Of 200 patients with aSAH who survived to day 7 and were included for DCI analysis, 39% cases were complicated with DCI. The Hijdra scale was the best predictor for DCI, with a receiver operating characteristic area under the curve (ROCAUC) of 0.80 (95% confidence interval [CI], 0.74–0.85) compared to other scales (Fisher grade 0.52 (95% CI, 0.47–0.59) modified Fisher grade: 0.67 (95% CI, 0.60–0.73); Claassen Scale: 0.66 (95% CI, 0.59–0.72) and BNI Scale: 0.63 (95% CI, 0.56–0.70)). The IVH score was the most effective grading system for predicting acute hydrocephalus, with a ROCAUC of 0.85 (95% CI, 0.79–0.89). In multivariate analysis, the Hijdra scale was the best predictor of the occurrence of DCI (hazard ratio, 1.18; 95% CI, 1.10–1.25). CONCLUSIONS Although these results have yet to be prospectively confirmed, our findings suggest that the Hijdra scale may be a good predictor of DCI and could be useful in daily clinical practice.

Purpose: Each summer, many vacationers enjoy the Mediterranean Sea shores. Among the recreational nautical activities, motorboat cruise is a popular choice that leads to a significant number of thoracolumbar spine fractures at our clinic. This phenomenon seems to be underreported, and its injury mechanism remains unclear. Here, we aim to describe the fracture pattern and propose a possible mechanism of injury. Methods: We retrospectively reviewed the clinical, radiological, and contextual parameters of all motorboat-related spinal fracture cases during a 14-year period (2006–2020) in three French neurosurgical level I centers bordering the Mediterranean Sea. Fractures were classified according to the AOSpine thoracolumbar classification system. Results: A total of 79 patients presented 90 fractures altogether. Women presented more commonly than men (61/18). Most of the lesions occurred at the thoracolumbar transition region between T10 and L2 (88.9% of the levels fractured). Compression A type fractures were seen in all cases (100%). Only one case of posterior spinal element injury was observed. The occurrence of neurological deficit was rare (7.6%). The most commonly encountered context was a patient sitting at the boat’s bow, without anticipating the trauma, when the ship’s bow suddenly elevated while crossing another wave, resulting in a “deck-slap” mechanism hitting and propelling the patient in the air. Conclusions: Thoracolumbar compression fractures are a frequent finding in nautical tourism. Passengers seated at the boat’s bow are the typical victims. Some specific biomechanical patterns are involved with the boat’s deck suddenly elevating across the waves. More data with biomechanical studies are necessary to understand the phenomenon. Prevention and safety recommendations should be given before motorboat use to fight against these avoidable fractures.

International audience; Background: Intracranial solitary fibrous tumour (iSFT) is an exceptional mesenchymal tumour with high recurrence rates. We aimed to analyse the clinical outcomes of newly diagnosed and recurrent iSFTs.Methods: We carried out a French retrospective multicentre (n = 16) study of histologically proven iSFT cases. Univariate and multivariate Cox models were used to estimate the prognosis value of the age, location, size, WHO grade, and surgical extent on overall survival (OS), progression-free survival (PFS), and local recurrence-free survival (LRFS).Results: Eighty-eight patients were included with a median age of 54.5 years. New iSFT cases were treated with gross tumour resection (GTR) (n = 75) or subtotal resection (STR) (n = 9) and postoperative radiotherapy (PORT) (n = 32, 57%). The median follow-up time was 7 years. The median OS, PFS, and LRFS were 13 years, 7 years, and 7 years, respectively. Forty-two patients experienced recurrence. Extracranial metastasis occurred in 16 patients. Median OS and PFS after the first recurrence were 6 years and 15.4 months, respectively. A higher histological grade was a prognosis factor for PFS (p = 0.04) and LRFS (p = 0.03). GTR influenced LRFS (p = 0.03).Conclusion: GTR provided benefits as a first treatment for iSFTs. However, approximately 40% of patients experienced relapse, which remains a challenging state.

Objective The aim of this study was to describe progestin-associated meningiomas’ characteristics, outcome and management. Material and methods We included 53 patients operated on and/or followed in the department for meningioma with progestin intake longer than one year and with recent drug discontinuation. Results Cyproterone acetate (CPA), nomegestrol acetate (NomA), and chlormadinone acetate (ChlA) were involved in most cases. Mean duration of progestin drugs intake was 17.5 years. Tumors were multiple in 66% of cases and were located in the anterior and the medial skull base in 71% of cases. Transitional subtype represented 16/25 tumors; 19 meningiomas were WHO grade I and 6 were grade II. The rate of transitional subtype and skull base location was significantly higher compared to matched operated meningioma general population. No difference was observed given WHO classification. But Ki67 proliferation index tends to be lower and 5/6 of the WHO grade II meningiomas were classified as WHO grade II because of brain invasion. Strong progesterone receptors expression was observed in most cases. After progestin discontinuation, a spontaneous visual recovery was observed in 6/10 patients. Under CPA (n = 24) and ChlA/NomA (n = 11), tumor volume decreased in 71% and 18% of patients, was stabilized in 25% and 64% of patients, and increased in 4% and 18% of patients, respectively. Volume outcome was related to meningioma location. Conclusions Outcome at progestins discontinuation is favorable but different comparing CPA versus ChlA-NomA and comparing tumor location. Long-term follow-up is required. In most cases, simple observation is recommended and surgery should be avoided.

International audience; PurposeTo report our experience of endoscopic endonasal obliteration of symptomatic sellar arachnoid cyst (SAC).MethodsFrom 2002 to 2019, we retrospectively reported the data of 17 cases of SAC operated in Timone University Hospital, Marseille, France. Preoperative clinical findings were collected including main symptoms, visual function and endocrinological assessment. Surgical procedure was homogeneous and consisted in endonasal fully endoscopic surgical obliteration of the cyst cavity with fat graft. Post-operative outcomes, complication and follow-up was reported.ResultsVisual disorders and/or headaches were the main symptoms. Our technique provided improvement for 83.3% of the patients suffering from visual disturbance and for 87.5% of those suffering from headaches. We reported 2 cases of cerebrospinal fluid (CSF) leakage (11.8%), but no meningitis. One case of definitive diabetes insipidus occurred and one case of postoperative syndrome of inappropriate antidiuretic hormone secretion was temporary. There was one case of recurrence reported. The mean follow-up was 39 months.ConclusionPatients with symptomatic SAC can be treated successfully by endoscopic endonasal obliteration of the cyst. This simple technique offers true benefits for the patients without craniotomy, but the complication rate remains high especially with the risk of CSF leakage. Special attention to skull base opening and closing could reduce this risk.

Transsphenoidal surgery is the first-line treatment for acromegaly. However, several factors can modify surgical remission rates, such as the initial hormone levels, the size and invasiveness of the tumor, and the degree of experience of the surgeon. Physicians treating patients with acromegaly should thus consider how to improve surgical remission rates. As stated in recent guidelines, the major point is to consider that any patient with acromegaly should be referred to an expert neurosurgeon to maximize the chances of surgical sure. The benefits of presurgical medical treatment, mainly using somatostatin receptor ligands (SRLs), given 3 to 6 months before surgery, remain controversial. By normalizing growth hormone and insulin-like growth factor 1 levels, SRLs may improve the overall condition of the patient, thus decreasing anesthetic and surgical complications. By decreasing the tumor size and modifying the consistency of the tumor, SRLs might also make surgical excision easier. This is however theoretical as published data are contradictory on both points, and only limited data support the use of a systematical presurgical medical treatment. The aim of this review is to analyze the potential benefits and pitfalls of using presurgical medical treatment in acromegaly in view of the contradictory literature data. We also attempt to determine the profile of patients who might most benefit from this presurgical medical treatment approach as an individualized therapeutic management of acromegaly.

International audience; BackgroundAccurate screw placement remains challenging, especially in the cervical spine. We present our first experience of minimally invasive posterior cervical and upper thoracic pedicle screw fixation in the lower cervical spine.MethodsThis study reports a case series of patients, undergoing posterior percutaneous pedicle fixation using Cirq robotic assistance coupled to the Airo intraoperative computed tomography scan and Brainlab navigation system. Routine computed tomography was performed on postoperative day 2 to evaluate pedicle screw placement. The effective dose was calculated.ResultsBetween February 2020 and December 2020, 7 patients (4 men and 3 women) were treated. The mean age was 58.8 years (range, 29–75 years). Fixation was performed with a cannulated PASS OCT Reconstruction System (Medicrea). Overall, 28 screws were placed within cervical and upper thoracic pedicles. According to the Neo and Heary classification, 85.7% were rated as acceptable and 14.3% as poor. The radiation dose received by the patient was 9.1 mSv (range, 7.7–10.6 mSv). The radiation dose received by the surgical staff was 0 mSv. The postoperative course was excellent.ConclusionsPosterior miniopen fixation using Cirq robotic assistance coupled with an intraoperative computed tomography navigation system is a major innovation that can improve the accuracy of pedicle screw positioning, with acceptable patient radiation and reduced surgical team exposure.

International audience; Recurrent or high-grade meningiomas are an unmet medical need. Recently, we demonstrated that targeting mTOR by everolimus was relevant both in vitro and in humans. However, everolimus induces an AKT activation that may impact the anti-proliferative effect of the drug. Moreover, the MAP kinase pathway was shown to be involved in meningioma tumorigenesis. We therefore targeted both the Pi3k-AKT-mTOR and MAP kinase pathways by using combinations of the Pi3k inhibitor alpelisib and the MEK inhibitor trametinib. Our study was performed in vitro on the human meningioma cell lines and on a large series of primary cultures providing from 63 freshly operated meningiomas including 35 WHO grade 1, 23 grade 2, and five grade 3, half of which presented a NF2 genomic alteration. Alpelisib induced a higher inhibitory effect on cell viability and proliferation than everolimus in all cell lines and 32 randomly selected tumors no matter the genomic status, the histological subtype or grade. Trametinib also strongly inhibited cell proliferation and induced AKT activation. Combined treatment with alpelisib plus trametinib reversed the AKT activation induced by trametinib and induced an additive inhibitory effect irrespective of the cell lines or tumor features. Co-targeting pathways seems promising and may be considered particularly for aggressive meningioma

OBJECTIVE The role of surgery in the treatment of malignant gliomas in the elderly is not settled. The authors conducted a randomized trial that compared tumor resection with biopsy only—both followed by standard therapy—in such patients. METHODS Patients ≥ 70 years of age with a Karnofsky Performance Scale (KPS) score ≥ 50 and presenting with a radiological suspicion of operable glioblastoma (GBM) were randomly assigned between tumor resection and biopsy groups. Subsequently, they underwent standard radiotherapy during the first years of the trial (2008–2017), with the addition of adjunct therapy with temozolomide when this regimen became standard (2017–2019). The primary endpoint was survival, and secondary endpoints were progression-free survival (PFS), cognitive status (Mini-Mental State Examination), autonomy (KPS), quality of life (European Organisation for Research and Treatment of Cancer [EORTC] QLQ-C30 and QLQ-BN20), and perioperative morbidity and mortality. RESULTS Between 2008 and 2019, 107 patients from 9 centers were enrolled in the study; 101 were evaluable for analysis because a GBM was histologically confirmed (50 in the surgery arm and 51 in the biopsy arm). There was no statistically significant difference in median survival between the surgery (9.37 months) and the biopsy (8.96 months, p = 0.36) arms (adjusted HR 0.79, 95% CI 0.52–1.21, p = 0.28). However, the surgery group had an increased PFS (5.06 vs 4.02 months; p = 0.034) (adjusted HR 0.50, 95% CI 0.32–0.78, p = 0.002). Less deterioration of quality of life and KPS score evolution than in the biopsy group was observed. Surgery was not associated with increased mortality or morbidity. CONCLUSIONS This study suggests that debulking surgery is safe, and—compared to biopsy—is associated with a less severe deterioration of quality of life and autonomy, as well as a significant although modest improvement of PFS in elderly patients suffering from newly diagnosed malignant glioma. Although resection does not provide a significant survival benefit in the elderly, the authors believe that the risk/benefit analysis favors an attempt at optimal tumor resection in this population, provided there is careful preoperative geriatric evaluation. Clinical trial registration no.: NCT02892708 (ClinicalTrials.gov)

Ventriculoperitoneal shunt (VPS) is an adequate treatment for congenital hydrocephalus or chronic hydrocephalus in adults. Yet, it is a surgery associated with a significant rate of complications amongst neurosurgical procedures, with frequent shunt obstructions and infections. We report the first-ever case of peritonitis caused by Roseomonas mucosa, shortly after the revision of a VPS ventricular catheter. Hardware removal and proper antibiotic therapy led to the patient's recovery. Roseomonas mucosa is an opportunistic skin pathogen with an antibiotic resistance profile to many beta-lactamines and a tropism for indwelling catheters and post-operative period. Nowadays, it should be taken into account in case of infection of indwelling catheters and for some implantable medical devices.

Background Odontoid fractures are the most common lesions of the upper cervical spine in patients >70 years old. These fractures are associated with frequent comorbidities, and minimally invasive techniques might have the potential to reduce postoperative complications while ensuring better precision. The aim of this study was to report an innovative technique and preliminary results of minimally invasive atlantoaxial fixation using a three-dimensional intraoperative navigation system and percutaneous approach. Methods This retrospective study included 5 consecutive patients with an acute traumatic odontoid type II fracture managed using a percutaneous Harms fixation under three-dimensional intraoperative navigation guidance. Results C1 lateral mass screws and C2 isthmus screws were successfully placed in all patients. In all cases (100%), adequate screw positioning with no medial breach and no transverse foramen obstruction was observed. No intraoperative complications, such as injury of the vertebral artery, spinal nerve root, or spinal cord, occurred. None of the 5 patients received blood transfusion during or after the procedure. During the follow-up period (mean, 11.2 months; range, 5-16 months), 4 patients (80%) demonstrated a favorable clinical recovery, and only 1 patient required occasional medication for moderate pain. Mean radiation exposure was 4.83 mSV for each patient and 0 mSv for surgical staff. Conclusions Minimally invasive atlantoaxial fixation using an intraoperative three-dimensional navigation system is a safe and effective alternative to the conventional approach that reduces postoperative morbidity.

Simple Summary Craniopharyngiomas (CPs) currently represent one of the most challenging diseases to deal with in the group of skull base tumors. Due to their location near, within, or surrounding the pituitary gland and stalk, CPs can be revealed by pituitary tumor syndrome and/or symptoms of hormonal deficiencies. Furthermore, surgery, which represents the first-line therapy, almost always results in hypopituitarism, diabetes insipidus and, in the case of hypothalamic involvement by the tumor, the occurrence of hypothalamic syndrome. The latter is characterized by intractable weight gain associated with severe morbid obesity, memory impairment, attention deficit, reduced impulse control and, eventually, increased risk of cardiovascular and metabolic disorders. Recent progress made in the understanding of the molecular pathways involved in CPs tumorigenesis paves the way for promising alternative therapeutic approaches and diagnostic procedures. Taken together, they lay the groundwork for new paradigms in the management of CPs in adults. Abstract Craniopharyngiomas (CPs) are rare tumors of the skull base, developing near the pituitary gland and hypothalamus and responsible for severe hormonal deficiencies and an overall increase in mortality rate. While surgery and radiotherapy represent the recommended first-line therapies for CPs, a new paradigm for treatment is currently emerging, as a consequence of accumulated knowledge concerning the molecular mechanisms involved in tumor growth, paving the way for anticipated use of targeted therapies. Significant clinical and basic research conducted in the field of CPs will undoubtedly constitute a real step forward for a better understanding of the behavior of these tumors and prevent associated complications. In this review, our aim is to summarize the multiple steps in the management of CPs in adults and emphasize the most recent studies that will contribute to advancing the diagnostic and therapeutic algorithms.

Objective: To assess the long-term surgical results on cranial nerve (CN) function and tumor control in patients harboring cerebellopontine angle (CPA) and petroclival area (PCA) epidermoid cysts (EC).Methods: This is a retrospective cohort study about 56 consecutive patients operated on for a CPA or PCA EC between January 2001 and July 2019 in six participating French cranial base referral centers.Results: Sixteen patients (29%) presented a PCA EC, and 40 a CPA EC (71%). The median clinical and radiological follow-up was 46 months (range 0-409). Preoperative CN disorders were present in 84% of patients (n=47), 72% of them experienced CN deficits improvement at last follow-up consultation (n=34) : 60% of cochlear and vestibular deficits (n=9/15 in both groups), 67% of trigeminal neuralgia (n=10/15), 53% of trigeminal hypoesthesia (n=8/15), 44% of lower cranial nerve disorders (n=4/9), 38% of facial nerve deficits (n=5/8), and 43% of oculomotor deficits (n=3/7) improved or were cured after surgery. New postoperative CN deficits occurred in 48% of patients (n=27). Most of them resolved at last follow-up, except for cochlear deficits which improved in only 14% of cases (n = 1/7). Twenty-six patients (46 %) showed evidence of tumor progression after a median duration of 63 months (range 7-210). Extent of resection, tumor location and tumor size were not associated with the occurrence of new postoperative CN deficit nor tumor progression. Conclusion: A functional nerve-sparing resection of posterior fossa EC is an effective strategy to optimize the results on preexisting CN deficits and reduces the risk of permanent de novo deficits.

Low intensity pulsed ultrasound in combination with microbubbles can be used to temporarily disrupt the blood-brain barrier (BBB). A phase 1/2 clinical study (NCT03744026) was initiated to demonstrate the safety and efficacy of BBB disruption using an implantable ultrasound system (SonoCloud-9) in patients with recurrent glioblastoma receiving carboplatin chemotherapy. The SonoCloud-9 device, which contains nine, 1-MHz, 10-mm diameter ultrasound emitters (Carthera, Paris, France) was placed at the end of tumor resection and replaced the bone flap. The device was activated 9-14 days after surgery for a duration of 270 seconds every four weeks until progression or treatment completion, concomitantly with IV DEFINITY microbubbles (10 ml/kg, Lantheus, Billerica, US). The Phase 1 cohort consisted of an escalation of BBB disruption volume by activation of 3 (n = 3), 6 (n = 3), then 9 (n = 3) emitters of the device. Dose limiting toxicity (DLT) was assessed during the first two weeks after the 1st sonication. A subsequent expansion cohort consisted of patients treated with nine emitters in which the primary endpoint was assessment of BBB opening on MRI using gadolinium (< 1 hr after sonication). All patients received carboplatin either after (n = 21) or before (n = 12) device activation to disrupt the BBB. In addition, a sub-study was performed to investigate carboplatin concentration enhancement in the peritumoral region with sonication at time of device implantation. Study accrual is complete with 33 patients having been implanted and received at least one sonication. A total of 101 sonications were performed (range = 1-10 sonication sessions/patient). No DLTs were observed. Five serious adverse events (all resolved) were considered as possibly related to the study procedure. BBB disruption was confirmed by gadolinium enhancement after sonication. In three patients who underwent intraoperative sonication and carboplatin administration, a 7.58-fold increase in brain/plasma drug levels was demonstrated. Updated survival results will be presented.

We aimed to identify genomic drivers of glioblastoma inevitable recurrence.Ten pairs of initial and recurrent frozen IDHwt glioblastoma samples were screened by CGH Array. Next Generation Sequencing (NGS) was then performed on an enriched cohort of 19 pairs. MPDZ alterations were analyzed using TCGA dataset.Nineteen IDHwt glioblastoma patients were included. Median age was 54.5 y/o (37.2-72.8). Using CGH array, unsupervised analysis aggregated the cohort by paired initial and recurrent tumors. Only 44% of CGH Array alterations were conserved at recurrence (amplifications: 55%; deletions: 30%). Two regions (including FPR1, 2 and 3) were lost at relapse: 19q13.33 and 19q13.41. MPDZ and 25 other genes were altered in ≥20% of recurrent tumors. NGS analysis of 29 candidate genes revealed 4 genes with pathogenic mutations: (FPR2, REL, TYRP1 and MPDZ). MPDZ (Multiple PDZ Domain Crumbs Cell Polarity Complex Component) was altered by two pathogenic mutations occurring at relapse. Using TCGA dataset we observed that a lower MPDZ mRNA expression was associated with IDHwt (p 0.001) and grade IV (p 0.001) gliomas. Finally, a low mRNA MPDZ expression was significantly correlated to poor overall survival in both IDHwt and IDH mutated gliomas, reinforcing the potential pejorative impact of MPDZ loss.Our results suggest that MPDZ is more frequently altered at relapse after radio-chemotherapy in glioblastoma IDHwt patients, suggesting that MPDZ impairment could contribute to the systematic resistance of these tumors opening new therapeutic perspectives.

Background: Forty percent of somatotroph tumors harbor recurrent activating GNAS mutations, historically called the gsp oncogene. In gsp-negative somatotroph tumors, GNAS expression itself is highly variable, those with GNAS overexpression most resemble phenotypically those carrying the gsp oncogene. GNAS is monoallelically expressed in the normal pituitary due to methylation-based imprinting. We hypothesize that changes in GNAS imprinting of gsp-negative tumors affect GNAS expression levels and tumorigenesis. Methods: We characterized the GNAS locus in two independent somatotroph tumor cohorts: one of 23 tumors previously published (PMID: 31883967) and classified by pan-genomic analysis, and a second with 82 tumors. Results: Multi-omics analysis of the first cohort identified a significant difference between gsp-negative and gsp-positive tumors in the methylation index at the known differentially methylated region (DMR) of the GNAS A/B transcript promoter, which was confirmed in the larger series of 82 tumors. GNAS allelic expression was analyzed using a polymorphic Fok1 cleavage site in 32 heterozygous gsp-negative tumors. GNAS expression was significantly reduced in the 14 tumors with relaxed GNAS imprinting and biallelic expression, compared to 18 tumors with monoallelic expression. Tumors with relaxed GNAS imprinting showed significantly lower SSTR2 and AIP expression levels. Conclusion: Altered A/B DMR methylation was found exclusively in gsp-negative somatotroph tumors. 43% of gsp-negative tumors showed GNAS imprinting relaxation, which correlated with lower GNAS, SSTR2 and AIP expression, indicating lower sensitivity to somatostatin analogues and potentially aggressive behavior.

Although the reduction of traumatic fractures of the thoracolumbar spine is of good quality during conventional so-called open procedures, the alternative minimally invasive approach also appears to confer good results. The aim of this study was to measure the radiological parameters before and after minimally invasive surgery, in order to assess the quality of the reduction of thoracolumbar compression fractures.This retrospective, monocentric study included 112 patients with a mean age of 48.9 years, presenting with 135 type A thoracolumbar compression fractures treated by a posterior minimally invasive surgical approach comprising vertebral augmentation or posterior osteosynthesis or a mixed procedure.The parameters analyzed were significantly lower whatever the procedure in the immediate postoperative period. Mean regional and local kyphosis, posterior wall displacement, and mean vertebral height were significantly lower (p0.01). Fracture reduction was better when osteosynthesis was associated with vertebral augmentation. In the osteosynthesis subgroup with osteosynthesis hardware removal but without vertebral augmentation, we found a significant worsening of the regional kyphosis (p0.05).The management of thoracolumbar compression fractures by a posterior minimally invasive approach allows excellent fracture reduction with a restoration of the spinal canal, vertebral height and kyphosis.IV.

2049 Background: Low intensity pulsed ultrasound (LIPU) in conjunction with intravenous microbubbles can transiently and reversibly disrupt the blood-brain barrier (BBB), allowing for an increase in the tissue concentration of chemotherapy agents in the brain. Mass spectrometry data from preclinical models (mouse, swine) showed a > 5x enhancement in carboplatin brain concentrations, which correlated well with the spatial distribution of a Gadolinium (Gd) contrast agent used for magnetic resonance imaging (MRI). Methods: The primary objective of this phase I/IIa study (NCT03744026) was to demonstrate the safety of BBB disruption using LIPU in patients with recurrent glioblastoma. This study was a 3+3 design using escalating numbers (3, 6, 9) of activated 1 MHz ultrasound emitters. Nine patients were treated in the escalation phase and another 12 patients were treated with 9 emitters in the expansion phase. Eligibility included recurrent GBM (any recurrence) with a maximum tumor size of < 70 mm. The SonoCloud-9 device (CarThera, Paris, France) was implanted during tumor debulking/resection surgery and replaced the bone flap, with the device targeting the tumor and surrounding peritumoral brain. The device was activated every four weeks for a duration of 270 seconds, concomitantly with IV DEFINITY microbubbles (10 ml/kg), to disrupt the BBB prior to administration of carboplatin (AUC 4-6). MRI was performed to verify safety and evaluate efficacy of BBB disruption with Gd enhancement. Results: No DLTs were observed. The overall tolerance of the SonoCloud-9 implant was good, with two transient, manageable grade 3 wound infections and one grade 1 acquired meningocele event considered as probably related to the overall procedure. The most frequent neurologic adverse events were grade 1 blurred vision (5%) and dizziness (5%). Conclusions: Significant Gd enhancement was observed after more than 90% of sonication sessions, suggesting effective BBB disruption and carboplatin enhancement. Clinical trial information: NCT03744026.

e14036 Background: “Biopsy only” GBM patients is an understudied group of patients associated to a poor outcome, which has been reported to represent 21% of histologically confirmed GBM in the US National Cancer Data Base. Pattern of care included radiotherapy-temozolomide (RT-TMZ) standard regimen completed in 15% of patients, any other form of oncologic treatment in 60%, and supportive care alone in 25% of patients (Kole, Cancer 2016). Our objective was to explore heterogeneity of inoperable GBM patients group, both for patients characteristics, pattern of care planned and completed, functional and survival outcome. Methods: Patients with inoperable GBM included in a prospective regional glioma cohort initiated in 2014 were retrospectively reviewed for patients characteristics, MRI finding, treatment allocation and delivery. Functional independency analyzed as a cumulative time of KPS≥70, PFS and OS were analyzed. Results: Of 535 patients referred to our center, 449 patients were included at initial surgery, of which 158 patients (35%) underwent biopsy only. 18 patients were excluded for missing data leaving 139 patients for the present analysis. 54 (39%) were referred to RT-TMZ (50 patients completed concomitant treatment), 68 (49%) considered unfitted for RT received chemotherapy upfront (CT-UF) (of which 3 were subsequently referred to RT), 17 (12%) referred to palliative care only (PC). Groups differed at baseline for age (mean 60, 68, 69y for RT-TMZ, CT-UF, PC respectively); for KPS (70, 60, 50 for RT-TMZ, CT-UF, PC respectively); for mean tumor surface (793, 1420, 1412 cm2 for RT-TMZ, CT-UF, PC); for tumor extension (bilateral in 6.4% and 29.3% for RT-CT and CT-UF respectively); for steroid intake (45, 60, 100 mg daily respectively). Median OS was 14 months (95% CI, 9.65-18.71), 8 months (95% CI, 4.62-7.67), 2 months (95% CI, 0.67-3.33) for RT-TMZ, CT-UF, PC respectively. Of importance, mean duration of functional independence was of 8.3 months, 2.1 months, and 0.1 month for RT-TMZ, CT-UF, and PC respectively; 33/139 (24%) of the patients experienced functional independency for more than 40% of their life time. Conclusions: Inoperable GBM constitute a large and heterogeneous population in which more than 1/3 of the patients are amenable to standard of care, with survival outcome similar to the one of patients who underwent surgery. Patients considered unfit for RT-CT at diagnosis fail to be referred subsequently to RT after CT and exhibit a poor survival outcome that deserve new effective treatments. Cumulative duration of functional independence is limited and should be considered as part of treatment evaluation.

Objective A relative can be an asset in dealing with chronic illnesses, such as acromegaly, where quality of life (QoL) is altered even after remission. However, it has been shown that quality of life of caregivers can also be impacted. Our main objective was to compare the perception of acromegaly in remission in the patient–relative dyad. Methods In this observational study, 27 patients in remission and relatives were first asked to complete QoL, anxiety/depression and coping strategy questionnaires. Then, the patient’s body image and self-esteem were evaluated from both the patient’s and the relative’s point of view using the same questionnaires with modified instructions. Results Relatives had overall an accurate estimation of patient body image using the Figure Rating Scale by Stunkard. However, there were wide variations between the patient’s and the relative’s responses regarding self-esteem and body perception. The QoL of relatives was not altered and was significantly higher in the social domain than for the patient. Conclusions Our results show that relatives require education concerning all the steps involved in the management of acromegaly, as they likely do not fully understand the sequelae of acromegaly.

Background: Associations between progestins and meningiomas is now well established. While the link between cyproterone acetate (CA) and meningioma was thoroughly studied, there is far less available data regarding the link between chlormadinone acetate (CHA) or nomegestrol acetate (NA) and risk of intracranial meningiomaMethods: We are presenting a series of 28 patients diagnosed with single or multiple meningiomas while treated with CHA-NA, in which the clinical and radiological course were analyzed after treatment discontinuation.Results: 28 women, with a mean age of 56 years old, were diagnosed with one or multiple meningioma while being treated with either CHA or NA. After stopping treatment, 89.3% showed either tumor shrinkage or tumor stabilization on follow-up MRIs. Multiple meningiomas were more likely observed in patients with long periods of treatment (>10 years, p 0.03) and seem to have a better clinical course (p 0.01). Most of the lesions were located on the skull base (55.4%). Four patients with multiple meningiomas showed discordant tumors evolution, with some tumors growing while others were decreasing. Most of the growing meningiomas were either convexity or midline lesions and more posteriorly located. Conclusion: Our study demonstrated a significant percentage of tumor diminution or stabilization after NA and CHA discontinuation. Therefore, treatment discontinuation with close monitoring should be the first measure taken if urgent surgery is not indicated. However, our results seem to be less encouraging than previously described in patients treated by CA, with more patients showing tumor growth despite treatment discontinuation. Further studies are needed to differentiate the effect of the different progestins treatment on meningiomas.

BACKGROUND/AIM Secondary leptomeningeal gliomatosis (LG) is a rare and severe progression pattern of glioma. Our objective was to evaluate the characteristics and outcome of patients with LG. PATIENTS AND METHODS We retrospectively reviewed 31 patients diagnosed with secondary LG. At the time of LG diagnosis, the median age of patients was 45 years. The histological grade was IV in 20 patients and II to III in 11 patients. As a first-line of therapy for LG, 22 patients received an oncological treatment: i) BCNU-temozolomide (TMZ) (n=15), ii) other type of chemotherapy (n=7), and iii) no treatment (supportive care) (n=9). RESULTS Following LG diagnosis, the median progression-free survival (PFS) and overall survival (OS) were 1.8 months [95% confidence interval (CI)=0.9-2.7] and 2.1 months (95%CI=1.3-3), respectively. The univariate analyses showed an improved OS with age of less than 45 years (p

Background Infectious aneurysm is a rare complication in intracranial aneurysm. Moreover, giant aneurysm is a rare entity in intracranial aneurysm. In the great majority of infectious intracranial aneurysms, vasculitis and/or endocarditis is associated. Case Description Here, we report the case of an 83-year-old man who developed a giant infectious intracranial aneurysm on the anterior communicating artery. This patient had never shown any intracranial bleeding. A surgery was performed, and purulent liquid and aneurysm wall were removed during procedure. The bacteriologic analyses reported Campylobacter fetus. Conclusions This bacterium seems to be more and more frequent in North America and Europe, according to the current literature. Moreover, cases of mycotic extracranial aneurysm were reported. Here we report the first case of intracranial giant infectious aneurysm in an adult patient, without any endocarditis or vasculitis. This new entity could be the cause of a bacterial graft on an asymptomatic giant preexisting intracranial aneurysm or a consequence of campylobacteriosis.

Background: Most of tuberculum sellae meningiomas (TSM) show asymmetric growth. They are usually resected through ipsilateral approaches. The access of the inferior–medial side of the ipsilateral optic nerve might be challenging, which result in increased manipulation of the compromised optic nerve. The contralateral approach has been described to avoid these technical difficulties.Objective: Assessing the long term visual and olfactory outcome, as well as recurrence rate in patients operated for TSM through ipsi- or contralateral approaches.Methods: Single center retrospective cohort study about 94 patients operated on between March 2000 and April 2018.Results: 70% of the preoperative visual acuity loss totally resolved (44%) or showed varying degrees of improvement (26%) after surgery. Seventy-two percent of the preoperative visual field defects evolved favorably (44% recovery, 28% improvement). Eight patients showed aggravated visual disturbances (9%). A contralateral approach seemed to be predictive of visual field defects improvement after surgery (OR=0.4), with borderline significant results (p=.08). There was a higher rate of postoperative olfactory nerve impairment after a contralateral approach (37%vs17%, p=.03). Total removal of the tumor fragment entering the optic canal was accomplished in 96% in the contralateral vs 75% in the ipsilateral group (p=.04). The 2-, 5- & 7-year tumor progression free survival were 100% in the Simpson Grade 2 group, and 85% (n=17), 74% (n=11) & 67% (n=5) in the Simpson Grade 4 group, respectively (p=.00). Conclusion: Resection of tuberculum sellae meningiomas through a contralateral approach seems to provide better visual outcome and tumor control at the cost of increased olfactory nerve disorders.

Sacral fractures are underdiagnosed and often undertreated. We report the second case of presentation and surgical management of a 56-year-old man with traumatic sacral U-shape fracture secondary to a grand mal epileptic seizure. We then discuss risk factors and mechanism of such fracture in epileptic patients.

Background We aimed to improve the assessment of the drug activity in meningioma clinical trials based on the study of the 3D volume growth rate (3DVGR) in a series of aggressive meningiomas. We secondarily aimed to correlate 3DVGR study with patient outcome. Methods We performed a post hoc analysis based on volume data and 3DVGR extracted from CEVOREM study including 18 patients with 32 recurrent high-grade meningiomas and treated with everolimus and octreotide. The joint latent class model was used to classify tumor 3DVGR undertreatment. Results Class 1 includes lesions responding to treatment with decrease in volume in the first 3 months, and then a stabilization thereafter (9.5% of tumors) (mean pretreatment 3DVGR = 6.13%/month; mean undertreatment 3DVGR = −18.7%/month within 3 first months and −0.14%/month after the 3 first months). Class 2 includes lesions considered as stable or with a slight increase in volume undertreatment (65.5%) (mean pretreatment 3DVGR = 6.09%/month; undertreatment 3DVGR = −0.09% within the first 3 months). Class 3 includes lesions without 3DVGR decrease (25%) (mean pretreatment 3DVGR = 46.9%/month; mean undertreatment 3DVGR = 19.2%/month within the first 3 months). Patients with class 3 lesions had a significantly worse progression-free survival (PFS) rate than class 1 and 2 ones. Conclusions Tumor 3DVGR could be helpful to detect early signal of drugs antitumoral activity or nonactivity. This volume response classification could help in the assessment of drug activity in tumors with mostly volume stabilization and rare response as aggressive meningiomas even with a low number of patients in complement to 6 months PFS.

BACKGROUND Post-operative complications do occur in all neurosurgical departments, but the way they are defined, and their true incidence vary a lot. The aim of the present study is to objectively assess the morbidity and mortality related to all neurosurgical procedures performed in our department and provide insight on their main causes and identify key factors to reduce their incidence. METHODS Data were retrieved from a prospectively-maintained database regarding all patients undergoing a cranial or spinal neurosurgical procedure between November 2016 and April 2016 in the neurosurgical department in Timone University Hospital (APHMMarseille). Patients undergoing a functional, pediatric or interventional neuroradiological procedures were not included. RESULTS The medical records of a total number of 963 patients were analyzed. A postoperative complication occurred in 208 patients (21.6%) including 115 (26.6%) in the cranial surgery group and 93 (17.5%) in the spinal surgery group. A complication occurred 1.5 more frequently in the cranial than in the spinal surgery group. Cranial surgery is 1.5 times more at risk of complications than spinal surgery (p=0.007). Preoperative comorbidities (ASA score > 3 to 4) were significantly associated with the occurrence of complications (p