Search

In cancer research, murine models play a crucial role as highly valuable preclinical tools. Here, we present a protocol to generate a murine model of glioblastoma through the direct intracranial injection of tumor cells. We describe steps for cell culture, intracranial implantation, and standard-of-care treatments. We then detail procedures for monitoring tumor growth using bioluminescent imaging. For complete details on the use and execution of this protocol, please refer to Pelizzari-Raymundo et al. 1 ., Competing Interests: Declaration of interests E.C. is the founder of Thabor Therapeutics; D.P.-R. and E.C. are authors of the patent PCT/EP2023/050228—Compounds containing a hydroxyphenyl moiety and their use, 2022., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Intrinsic or environmental stresses trigger the accumulation of improperly folded proteins in the endoplasmic reticulum (ER), leading to ER stress. To cope with this, cells have evolved an adaptive mechanism named the unfolded protein response (UPR) which is hijacked by tumor cells to develop malignant features. Glioblastoma (GB), the most aggressive and lethal primary brain tumor, relies on UPR to sustain growth. We recently showed that IRE1 alpha (referred to IRE1 hereafter), 1 of the UPR transducers, promotes GB invasion, angiogenesis, and infiltration by macrophage. Hence, high tumor IRE1 activity in tumor cells predicts a worse outcome. Herein, we characterized the IRE1-dependent signaling that shapes the immune microenvironment toward monocytes/macrophages and neutrophils., Methods: We used human and mouse cellular models in which IRE1 was genetically or pharmacologically invalidated and which were tested in vivo. Publicly available datasets from GB patients were also analyzed to confirm our findings., Results: We showed that IRE1 signaling, through both the transcription factor XBP1s and the regulated IRE1-dependent decay controls the expression of the ubiquitin-conjugating E2 enzyme UBE2D3. In turn, UBE2D3 activates the NFκB pathway, resulting in chemokine production and myeloid infiltration in tumors., Conclusions: Our work identifies a novel IRE1/UBE2D3 proinflammatory axis that plays an instrumental role in GB immune regulation., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Ruptured middle cerebral artery aneurysm (MCAa) can lead to intracerebral hematoma, and surgical evacuation can be performed in these cases. MCAa can be treated by clipping or before by endovascular therapy (EVT). Our objective was to compare the impact on the functional outcome of MCAa in patients with intracerebral hematoma requiring evacuation., Methods: This is a multicenter, retrospective, cohort study with nine French neurosurgical units from January 1, 2013, to December 31, 2020. All participants were adult patients who required evacuation of an intracerebral hematoma. We looked for risk factors for poor outcomes by comparing the baseline characteristics and treatments performed by using the 6-month modified Rankin scale score. Poor outcomes were defined by an modified Rankin scale score of 3-6., Results: A total of 162 patients were included. A total of 129 (79.6%) patients were treated by microsurgery, and 33 (20.4%) patients were treated by EVT. In multivariate analysis, factors associated with poor outcomes included hematoma volume, realization of a decompressive craniectomy, occurrence of procedure-related symptomatic cerebral ischemia, occurrence of delayed cerebral ischemia, and EVT. In the propensity score matching analysis (n = 33 per group), poor outcomes were observed in 30% of the patients in the clipping group versus 76% in the EVT group (P < 0.001). These differences may have been related to a longer delay between hospital admission and hematoma evacuation in the EVT group., Conclusions: In the specific subgroup of ruptured MCAa with intracerebral hematoma that requires surgical evacuation, clipping with concomitant hematoma evacuation could provide better functional outcomes than EVT followed by surgical evacuation., (© 2023. Springer Science+Business Media, LLC, part of Springer Nature and Neurocritical Care Society.)

Background and Objectives: Spinal cord metastasis arising from an intracranial glioblastoma is a rare and late event during the natural course of the disease. These pathological entities remain poorly characterized. This study aimed to identify and investigate the timeline, clinical and imaging findings, and prognostic factors of spinal cord metastasis from a glioblastoma., Methods: Consecutive histopathological cases of spinal cord metastasis from glioblastomas in adults entered in the French nationwide database between January 2004 and 2016 were screened., Results: Overall, 14 adult patients with a brain glioblastoma (median age 55.2 years) and harboring a spinal cord metastasis were included. The median overall survival as 16.0 months (range, 9.8-22.2). The median spinal cord Metastasis Free Survival (time interval between the glioblastoma diagnosis and the spinal cord metastasis diagnosis) was 13.6 months (range, 0.0-27.9). The occurrence of a spinal cord metastasis diagnosis greatly impacted neurological status: 57.2% of patients were not ambulatory, which contributed to dramatically decreased Karnofsky Performance Status (KPS) scores (12/14, 85.7% with a KPS score ≤ 70). The median overall survival following spinal cord metastasis was 3.3 months (range, 1.3-5.3). Patients with a cerebral ventricle effraction during the initial brain surgery had a shorter spinal cord Metastasis Free Survival (6.6 vs 18.3 months, p = 0.023). Out of the 14 patients, eleven (78.6%) had a brain IDH-wildtype glioblastoma., Conclusions: Spinal cord metastasis from a brain IDH-wildtype glioblastoma has a poor prognosis. Spinal MRI can be proposed during the follow-up of glioblastoma patients especially those who have benefited from cerebral surgical resection with opening of the cerebral ventricles., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: Differentiating brain metastasis recurrence from radiation necrosis can be challenging during MRI follow-up after stereotactic radiotherapy. [ 18 F]-FDG is the most available PET tracer, but standard images performed 30 to 60 minutes postinjection provide insufficient accuracy. We compared the diagnostic performance and interobserver agreement of [ 18 F]-FDG PET with delayed images (4-5 hours postinjection) with the ones provided by standard and dual-time-point imaging., Methods: Consecutive patients referred for brain [ 18 F]-FDG PET after inconclusive MRI were retrospectively included between 2015 and 2020 in 3 centers. Two independent nuclear medicine physicians interpreted standard (visually), delayed (visually), and dual-time-point (semiquantitatively) images, respectively. Adjudication was applied in case of discrepancy. The final diagnosis was confirmed histologically or after 6 months of MRI follow-up. Areas under the receiver operating characteristic curves were pairwise compared., Results: Forty-eight lesions from 46 patients were analyzed. Primary tumors were mostly located in the lungs (57%) and breast (23%). The median delay between radiotherapy and PET was 15.7 months. The final diagnosis was tumor recurrence in 24 of 48 lesions (50%), with histological confirmation in 19 of 48 lesions (40%). Delayed images provided a larger area under the receiver operating characteristic curve (0.88; 95% confidence interval [CI], 0.75-0.95) than both standard (0.69; 95% CI, 0.54-0.81; P = 0.0014) and dual-time-point imaging (0.77; 95% CI, 0.63-0.88; P = 0.045), respectively. Interobserver agreement was almost perfect with delayed images ( κ = 0.83), whereas it was moderate with both standard ( κ = 0.48) and dual-time-point images ( κ = 0.61)., Conclusions: [ 18 F]-FDG PET with delayed images is an accurate and reliable alternative to differentiate metastasis recurrence from radiation necrosis in case of inconclusive MRI after brain stereotactic radiotherapy., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Quantification of dynamic and static parameters extracted from 3,4-dihydroxy-6-[ 18 F]-fluoro-L-phenylalanine ( 18 F-DOPA, FDOPA) positron emission tomography (PET)/computed tomography (CT) plays a critical role for glioma assessment. The objective of the present study was to investigate the impact of point-spread function (PSF) reconstruction on these quantitative parameters., Methods: Fourteen patients with untreated gliomas and investigated with FDOPA PET/CT were analyzed. The distribution of the 14 cases was as follows: 6 astrocytomas-isocitrate dehydrogenase-mutant; 2 oligodendrogliomas/1p19q-codeleted-isocitrate dehydrogenase-mutant; and 6 isocitrate dehydrogenase-wild-type glioblastomas. A 0-20-min dynamic images (8×15, 2×30, 2×60, and 3×300 s post-injection) and a 0-20-min static image were reconstructed with and without PSF. Tumoral volumes-of-interest were generated on all of the PET series and the background volumes-of-interest were generated on the 0-20-min static image with and without PSF. Static parameters (SUVmax and SUVmean) of the tumoral and the background volumes-of-interest and kinetic parameters (K1 and k2) of the tumoral volumes-of-interest extracted from using full kinetic analysis were provided. PSF and non-PSF quantitative parameters values were compared., Results: Thirty-three tumor volumes-of-interest and 14 background volumes-of-interest were analyzed. PSF images provided higher tumor SUVmax than non-PSF images for 23/33 VOIs [median SUVmax =3.0 (range, 1.4-10.2) with PSF vs. 2.7 (range, 1.4-9.1) without PSF; P<0.001] and higher tumor SUVmean for 13/33 volumes-of-interest [median SUVmean =2.0 (range, 0.8-7.6) with PSF vs. 2.0 (range, 0.8-7.4) without PSF; P=0.002]. K1 and k2 were significantly lower with PSF than without PSF [respectively median K1 =0.077 mL/ccm/min (range, 0.043-0.445 mL/ccm/min) with PSF vs. 0.101 mL/ccm/min (range, 0.055-0.578 mL/ccm/min) without PSF; P<0.001 and median k2 =0.070 min -1 (range, 0.025-0.146 min -1 ) with PSF vs. 0.081 min -1 (range, 0.027-0.180 min -1 ) without PSF; P<0.001]. Background SUVmax and SUVmean were statistically unaffected [respectively median SUVmax =1.7 (range, 1.3-2.0) with PSF vs. 1.7 (range, 1.3-1.9) without PSF; P=0.346 and median SUVmean =1.5 (range, 1.0-1.8) with PSF vs. 1.5 (range, 1.0-1.7) without PSF; P=0.371]., Conclusions: The present study confirms that PSF significantly increases tumor activity concentrations measured on PET images. PSF algorithms for quantitative PET/CT analysis should be used with caution, especially for quantification of kinetic parameters., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://dx.doi.org/10.21037/qims-21-742). The authors have no conflicts of interest to declare., (2022 Quantitative Imaging in Medicine and Surgery. All rights reserved.)

Raman spectroscopy is an imaging technique that has been applied to assess molecular compositions of living cells to characterize cell types and states. However, owing to the diverse molecular species in cells and challenges of assigning peaks to specific molecules, it has not been clear how to interpret cellular Raman spectra. Here, we provide firm evidence that cellular Raman spectra (RS) and transcriptomic profiles of glioblastoma can be computationally connected and thus interpreted. We find that the dimensions of high-dimensional RS and transcriptomes can be reduced and connected linearly through a shared low-dimensional subspace. Accordingly, we were able to predict global gene expression profiles by applying the calculated transformation matrix to Raman spectra and vice versa. From these analyses, we extract a minimal gene expression signature associated with specific RS profiles and predictive of disease outcome., (© 2021 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

Purpose: We aimed to compare spatial extent of high-grade subregions detected with combined [ 18 F]-dihydroxyphenylalanine ( 18 F-DOPA) PET and MRI to the one provided by advanced multimodal MRI alone including Contrast-enhanced (CE) and Perfusion weighted imaging (PWI). Then, we compared the accuracy between imaging modalities, in a per biopsy analysis., Methods: Participants with suspected diffuse glioma were prospectively included between June 2018 and September 2019. Volumes of high-grade subregions were delineated respectively on 18 F-DOPA PET and MRI (CE and PWI). Up to three per-surgical neuronavigation-guided biopsies were performed per patient., Results: Thirty-eight biopsy samples from sixteen participants were analyzed. Six participants (38%) had grade IV IDH wild-type glioblastoma, six (38%) had grade III IDH-mutated astrocytoma and four (24%) had grade II IDH-mutated gliomas. Three patients had intratumoral heterogeneity with coexisting high- and low-grade tumor subregions. High-grade volumes determined with combined 18 F-DOPA PET/MRI (median of 1.7 [interquartile range (IQR) 0.0, 19.1] mL) were larger than with multimodal MRI alone (median 1.3 [IQR 0.0, 12.8] mL) with low overlap (median Dice's coefficient 0.24 [IQR 0.08, 0.59]). Delineation volumes were substantially increased in five (31%) patients. In a per biopsy analysis, combined 18 F-DOPA PET/MRI detected high-grade subregions with an accuracy of 58% compared to 42% (p = 0.03) with CE MRI alone and 50% (p = 0.25) using multimodal MRI (CE + PWI)., Conclusions: The addition of 18 F-DOPA PET to multimodal MRI (CE and PWI) enlarged the delineation volumes and enhanced overall accuracy for detection of high-grade subregions. Thus, combining 18 F-DOPA with advanced MRI may improve treatment planning in newly diagnosed gliomas., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: The aim of this study was to assess the value of the FDOPA PET kinetic parameters extracted using full kinetic analysis for tumor grading with neuronavigation-guided biopsies as reference in patients with newly-diagnosed gliomas. Methods: Fourteen patients with untreated gliomas were investigated. Twenty minutes of dynamic positron-emission tomography (PET) imaging and a 20-min static image 10 min after injection were reconstructed from a 40-min list-mode acquisition immediately after FDOPA injection. Tumors volume-of-interest (VOI) were generated based on the MRI-guided brain biopsies. Static parameters (TBRmax and TBRmean) and kinetic parameters [K1 and k2 using full kinetic analysis with the reversible single-tissue compartment model with blood volume parameter and the time-to-peak (TTP)] were extracted. Performances of each parameter for differentiating low-grade gliomas (LGG) from high-grade gliomas (HGG) were evaluated by receiver-operating characteristic analyses (area under the curve; AUC). Results: Thirty-two tumoral VOI were analyzed. K1, k2, and TTP were significantly higher for HGG than for LGG (median K1-value = 0.124 vs. 0.074 ml/ccm/min, p = 0.025, median k2-value = 0.093 vs. 0.063 min -1 , p = 0.025, and median TTP-value = 10.0 vs. 15.0 min, p = 0.025). No significant difference was observed for the static parameters. The AUC for the kinetic parameters was higher than the AUC for the static parameters (respectively, AUC K1 = 0.787, AUC k2 = 0.785, AUC TTP = 0.775, AUC TBRmax = 0.551, AUC TBRmean = 0.575), significantly compared to TBRmax (respectively, p = 0.001 for K1, p = 0.031 for k2, and p = 0.029 for TTP). Conclusion: The present study suggests an additive value of FDOPA PET/CT kinetic parameters for newly-diagnosed gliomas grading., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Girard, Le Reste, Metais, Chaboub, Devillers, Saint-Jalmes, Jeune and Palard-Novello.)

In the past decades, many studies reported the presence of endoplasmic reticulum (ER)-resident proteins in the cytosol. However, the mechanisms by which these proteins relocate and whether they exert cytosolic functions remain unknown. We find that a subset of ER luminal proteins accumulates in the cytosol of glioblastoma cells isolated from mouse and human tumors. In cultured cells, ER protein reflux to the cytosol occurs upon ER proteostasis perturbation. Using the ER luminal protein anterior gradient 2 (AGR2) as a proof of concept, we tested whether the refluxed proteins gain new functions in the cytosol. We find that refluxed, cytosolic AGR2 binds and inhibits the tumor suppressor p53. These data suggest that ER reflux constitutes an ER surveillance mechanism to relieve the ER from its contents upon stress, providing a selective advantage to tumor cells through gain-of-cytosolic functions-a phenomenon we name ER to Cytosol Signaling (ERCYS)., (© 2021 The Authors. Published under the terms of the CC BY 4.0 license.)

Background: Ventriculitis, a dreaded complication of brain abscess, meningitis, and various neurosurgical procedures, has attracted limited attention in the medical literature., Methods: This is a retrospective, single-center study. We screened the medical files of all patients who had a brain imaging report that included the word "ventriculitis" during years 2005-2019. Only patients with clinical, microbiological, and imaging features of ventriculitis were included. Data were collected through a standardized questionnaire., Results: Ninety-eight patients fulfilled inclusion criteria: 42 women and 56 men, and the median age was 60 years (interquartile range, 48-68). The primary mechanism for ventriculitis was classified as follows: brain abscess (n = 29, 29.6%), meningitis (n = 27, 27.6%), intraventricular catheter-related (n = 17, 17.3%), post-neurosurgery (n = 13, 13.3%), and hematogenous (n = 12, 12.2%). The main neuroimaging features were intraventricular pus (n = 81, 82.7%), ependymal enhancement (n = 70, 71.4%), and intraventricular loculations (n = 15, 15.3%). The main pathogens were streptococci (n = 44, 44.9%), Gram-negative bacilli (n = 27, 27.6%), and staphylococci (n = 15, 15.3%). In-hospital and 1-year mortality rates were 30.6% (n = 30) and 38.8% (n = 38), respectively. Neurological sequelae were reported in 34 of 55 (61.8%) survivors, including cognitive impairment (n = 11), gait disturbances (n = 9), paresis (n = 7), behavior disorder (n = 6), and epilepsy (n = 5). On multivariate analysis, age >65 years, Glasgow Coma Scale score <13 at initial presentation, status epilepticus, hydrocephalus, and positive cerebrospinal fluid culture were associated with 1-year mortality. We built a scoring system to stratify patients with ventriculitis into low risk (12.5%), intermediate risk (36.5%), and high risk (71.4%) of death., Conclusions: Ventriculitis is a severe complication of brain abscess, meningitis, or neurosurgery, with an in-hospital mortality rate of 30% and neurological sequelae in 60% of survivors., (© The Author(s) 2021. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

A posterior cervical defect featuring exposed spinal and occipital bone can be covered in various ways. The "ideal" flap should be a low-morbidity, pedicled locoregional flap that can reach the occiput. Cervical adjuvant radiation therapy may limit the coverage options, because many pedicles are located in areas that are often irradiated. Here, we describe a new surgical technique; we used a skin perforator flap pedicled by the intercostal muscle to cover a posterior cervical defect in a patient with metastatic squamous cell lung carcinoma. This technique is a valuable option; the flap originated from outside the irradiated area and reached the occiput. It adds to the options for cervical coverage in patients who require head-and-neck reconstruction. EVIDENCE-BASED MEDICINE: Level V: opinions of respected authorities, based on clinical experience, descriptive studies, or reports of expert committees., (Copyright © 2020. Published by Elsevier Masson SAS.)

Glioblastoma multiforme (GBM) is the most severe primary brain cancer. Despite an aggressive treatment comprising surgical resection and radio/chemotherapy, patient's survival post diagnosis remains short. A limitation for success in finding novel improved therapeutic options for such dismal disease partly lies in the lack of a relevant animal model that accurately recapitulates patient disease and standard of care. In the present study, we have developed an immunocompetent GBM model that includes tumor surgery and a radio/chemotherapy regimen resembling the Stupp protocol and we have used this model to test the impact of the pharmacological inhibition of the endoplasmic reticulum (ER) stress sensor IRE1, on treatment efficacy., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Introduction: Several predictors have been described to early diagnose malignant middle cerebral artery infarction (MMI) and select patient for hemicraniectomy. Nevertheless, few studies have assessed them among patients with acute ischemic stroke undergoing mechanical endovascular thrombectomy (MET). The overall objective in this study was to evaluate these predictors in patients undergoing MET in the purpose to guide the medical care in the acute phase., Methods: We selected patients from a prospective local database which reference all patients eligible for treatment with Alteplase thrombolysis and/or mechanical endovascular thrombectomy in acute stroke. We investigated demographic, clinical, and radiological data. Multivariate regression analysis was used to identify clinical and imaging predictors of MMI., Results: In 32 months, 66 patients were included. Eighteen (27.3%) developed MMI. Malignant evolution was associated with: severity of neurological deficit and level of consciousness at admission, infarct size in DWI sequence and involvement of other vascular territories. Study groups didn't differ in terms of successful reperfusion. Two variables were identified as independent predictors of MMI: DWI infarct volume (p<0.001) and time to thrombectomy (p=0.018). A decision tree based on these two factors was able to predict malignant evolution with high specificity (100%) and sensibility (73%)., Conclusion: Our study proposes a practical decision tree including DWI lesion volume and delay before thrombectomy to early and accurately predict MMI in a subgroup of patients with MCA infarction undergoing MET regardless to the status of reperfusion., (Copyright © 2020. Published by Elsevier Masson SAS.)

Introduction: 3,4-dihydroxy-6-[18F]fluoro-L-phenylalanine (FDOPA) uptake quantification in glioma assessment can be distorted using a non-optimal time frame binning of time-activity curves (TAC). Under-sampling or over-sampling dynamic PET images induces significant variations on kinetic parameters quantification. We aimed to optimize temporal time frame binning for dynamic FDOPA PET imaging., Methods: Fourteen patients with 33 tumoral TAC with biopsy-proven gliomas were analysed. The mean SUVmax tumor-to-brain ratio (TBRmax) were compared at 20 min and 35 min post-injection (p.i). Five different time frame samplings within 20 min were compared: 11x10sec-6x15sec-5x20sec-3x300sec; 8x15sec- 2x30sec- 2x60sec- 3x300sec; 6x20sec- 8x60sec- 2x300sec; 10x30sec- 3x300sec and 4x45sec- 3x90sec- 5x150sec. The reversible single-tissue compartment model with blood volume parameter (VB) was selected using the Akaike information criterion. K1 values extracted from 1024 noisy simulated TAC using Monte Carlo method from the 5 different time samplings were compared to a target K1 value as the objective, which is the average of the K1 values extracted from the 33 lesions using an imaging-derived input function for each patient., Results: The mean TBRmax was significantly higher at 20 min p.i. than at 35 min p.i (respectively 1.4 +/- 0.8 and 1.2 +/- 0.6; p <0.001). The target K1 value was 0.161 mL/ccm/min. The 8x15sec- 2x30sec- 2x60sec- 3x300sec time sampling was the optimal time frame binning. K1 values extracted using this optimal time frame binning were significantly different with K1 values extracted from the other time frame samplings, except with K1 values obtained using the 11x10sec- 6x15sec -5x20sec-3x300sec time frame binning., Conclusions: This optimal sampling schedule design (8x15sec- 2x30sec- 2x60sec- 3x300sec) could be used to minimize bias in quantification of FDOPA uptake in glioma using kinetic analysis., Competing Interests: The authors have declared that no competing interests exist.

Introduction: Subarachnoid hemorrhage (SAH) from intracranial aneurysm rupture is an unpredictable event responsible for significant morbidity and mortality. Despite inconsistencies, some studies suggest a potential role of climate conditions in SAH onset. The purpose of this study was to determine the impact of climatic and lunar factors on onset of SAH in an oceanic climate such as that of Brittany, France., Methods: All adults with SAH admitted to the neurosurgery department and intensive care unit of the University Hospital of Rennes (France) between January 1st, 2011 and December 31st, 2012 were included. Meteorological variables, their variations, lunar phases and tidal coefficients were compared between days with and without SAH., Results: We retrospectively included 295 patients with SAH. Mean minimum temperature was significantly lower during days with SAH (7.7±4.7°C versus 8.3±4.6°C; P=0.039); temperature variation between 2 successive days was significantly greater for days with SAH (8.6±4.1°C versus 7.9±3.8°C; P<0.01). Multivariate analysis showed that a 2-day temperature drop greater than or equal to 8°C was associated with 35% increased risk of SAH (odds ratio 1.35 [1.03-1.77]). There were no significant effects of other meteorological variables, lunar phase or tidal coefficient on SAH occurrence., Conclusion: Low temperature and sudden temperature drop were associated with increased occurrence of SAH in Brittany, France., (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)

The gold standard treatment of spinal dural arteriovenous fistulas (SDAVF) is surgical exclusion. The main surgical challenge is to localize the origin of the shunting vein and to ensure its complete exclusion. In that context, intra operative angiography technologies have been developed, such as fluorescein video angiography (FVA). The objective of this preliminary study was to assess the utility of FVA in SDAVF surgery through a short surgical series. We retrospectively studied the cases of six patients who had a FVA for a SDAVF. FVA was performed after dural opening and visualization of the suspected shunting vein. In 5 cases, FVA was performed after ligation to ensure the complete exclusion. In 2 cases, FVA was performed before the ligation to confirm the localization of the shunt. In 1 case, FVA was performed before and after ligation. FVA was judged useful in all cases to localize the origin of the shunting vein. FVA permitted to ensure the complete exclusion after ligation. No anaphylactic events were noticed. Our preliminary study suggests that fluorescein video angiography is feasible and helpful for SDAVF surgery., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Objective: Spinal dural arteriovenous fistulas (SDAVFs) are rare vascular spinal malformations. According to the reported data, surgery seems to result in better occlusion rates than endovascular treatment. However, the post-treatment evolution of neurological symptoms stratified by the treatment remains unknown. The main objective of the present study was to compare the clinical outcomes for patients according to the treatment method., Methods: The data from 63 patients with SDAVFs from 2000 to 2017 at 4 academic neurosurgical departments were retrospectively analyzed. Preoperative and postoperative examination neurological status was assessed using the Aminoff-Logue scale (ALS), which evaluates gait and micturition disturbances. Initial occlusion, late recurrence, and complications of the 2 techniques were also reviewed., Results: Patients who had undergone surgery and embolization improved clinically on the ALS (P = 0.0009), and no significant differences were found between the 2 techniques. Subgroup analysis using the ALS showed that patients who had undergone surgery and embolization without late recurrence improved (P < 0.0001 and P = 0.0334, respectively) and that patients who had undergone surgery or embolization with late recurrence did not improve. The initial occlusion rate was in favor of surgery, with 91.3% versus 70% for endovascular treatment (P = 0.050). The late recurrence rate was higher for embolization (21.4% vs. 9.1% for surgery; P = 0.28)., Conclusions: Surgery can be proposed as first-line treatment of SDAVFs after multidisciplinary discussion between neurosurgeons and neuroradiologists. The development of late recurrence negatively affects the neurological outcome of patients., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Aims: To compare the neurogenic lower urinary tract dysfunction (NLUTD) in patients with closed spinal dysraphism (CSD) versus patients with open spinal dysraphism (OSD) as well as their management patterns., Methods: A prospective cross-sectional study was conducted between September 2007 and December 2015 including all spina bifida patients seen at the multidisciplinary French national referral center for spina bifida. NLUTD and its management were compared between the OSD and CSD groups., Results: Three hundred and eighteen patients were included for analysis: 100 with a CSD (31.5%) and 218 with an OSD (68.6%). The prevalence of urinary incontinence did not differ significantly between the two groups (43% vs 52.8%; P = 0.11), the mean Qualiveen score was also similar (2.7 vs 2.5, P = 0.22). The voiding mechanism was clean intermittent catheterization, spontaneous voiding, suprapubic tube, and ileal conduit in 55% versus 44%; 29.8% versus 47%; 2.8% versus 3% and 11.9% versus 6% of OSD and CSD patients, respectively (P = 0.02). There were comparable prevalences of detrusor overactivity (36.5% vs 38.8%; P = 0.68) and impaired bladder compliance (34.9% vs 31.7%; P = 0.56) in both groups. Augmentation cystoplasty was more common in patients with OSD (32.1% vs 11%; P < 0.0001)., Conclusions: In this prospective cohort, NLUTD were more common in OSD with a higher rate of patients requiring a surgical treatment and a lower rate of patients with preserved spontaneous voiding. However, when present, NLUTD was as severe and troublesome in patients with closed versus open spinal dysraphism., (© 2018 Wiley Periodicals, Inc.)

Objective: Meningiomas that compress the optic nerve (ON) can lead to different visual outcomes depending on the segment of ON affected (intraorbital, canalicular, and intracranial). In this study, we performed a comprehensive comparison of the management options (surgery, radiation, or observation alone) for meningiomas compressing the ON, categorized by location and relation to the ON., Methods: MEDLINE, EMBASE, Web of Science, and the Cochrane Database of Systematic reviews databases were searched according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement. Data were extracted from the articles regarding anatomic location, initial visual impairment, surgical procedure, visual outcome, morbidity and mortality, gross total removal, and requirement for postoperative radiotherapy., Results: Of the 47 articles eligible for full-text reading, 9 surgical studies met our inclusion criteria. Data from 317 patient cases were extracted. In patients in whom the intracranial segment of the ON was impaired in isolation, 49% experienced visual improvement after surgery. When the meningioma affected the canalicular segment or intraorbital segment, visual improvement after surgery was 31% and 11%, respectively. Of patients who underwent surgery for the intraorbital segment of the ON, 56% experienced a decline in visual outcome., Conclusions: When a neurosurgeon deals with a meningioma compressing the ON, opening the optic canal is suggested if invasion is suspected on the preoperative imaging. Extra caution should be used when operating on meningiomas with ON sheath adhesion, given the higher evidence of postoperative visual worsening., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Translational medicine has been nurtured by the creation of M.D.-Ph.D. programs, a system that now needs to reinvent itself. Now, clinically oriented training programs targeting nonphysician scientists have opened new avenues to improve transdisciplinary approaches in health sciences., (Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

Brain arteriovenous malformations (AVM) are complex and highly challenging lesions, for which intra-operative indocyanin green fluorescence video angiography is widely used. Fluorescein video angiography (FVA) recently appeared as an alternative technique but the feasibility and usefulness of this technique is yet uncertain. This short series reports our preliminary experience of FVA in intracranial AVM surgery. We retrospectively studied the cases of seven patients who had FVA for an AVM surgery. The primary objective of this study was to assess the utility of FVA as judged by the surgeon. Secondary objectives were the evaluation of the tolerance of bolus injection of fluorescein in the context of cranial surgery, the comparison with ICG and the rate of complete removal. For each of the seven patients, FVA was performed after exposure of the AVM and before the resection; it was visualized directly through the eyepieces of the microscope and helped in the identification of arterial feeders and draining veins. In one case, post-resection FVA allowed the visualization of a residual shunt and the resection was completed. In two cases, ICG and FVA brought comparable information. The resection was complete in all cases, confirmed by post-operative imaging. There was no anaphylactic complication. This preliminary work suggests that FVA is a simple and well tolerated technique, comparable to ICG angiography. Prospective and larger studies are needed to confirm the clinical benefit of this tool., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Proteostasis imbalance is emerging as a major hallmark of cancer, driving tumor aggressiveness. Evidence suggests that the endoplasmic reticulum (ER), a major site for protein folding and quality control, plays a critical role in cancer development. This concept is valid in glioblastoma multiform (GBM), the most lethal primary brain cancer with no effective treatment. We previously demonstrated that the ER stress sensor IRE1α (referred to as IRE1) contributes to GBM progression, through XBP1 mRNA splicing and regulated IRE1-dependent decay (RIDD) of RNA Here, we first demonstrated IRE1 signaling significance to human GBM and defined specific IRE1-dependent gene expression signatures that were confronted to human GBM transcriptomes. This approach allowed us to demonstrate the antagonistic roles of XBP1 mRNA splicing and RIDD on tumor outcomes, mainly through selective remodeling of the tumor stroma. This study provides the first demonstration of a dual role of IRE1 downstream signaling in cancer and opens a new therapeutic window to abrogate tumor progression., (© 2018 The Authors. Published under the terms of the CC BY 4.0 license.)

We assessed prognostic factors in relation to OS from progression in recurrent glioblastomas. Retrospective multicentric study enrolling 407 (training set) and 370 (external validation set) adult patients with a recurrent supratentorial glioblastoma treated by surgical resection and standard combined chemoradiotherapy as first-line treatment. Four complementary multivariate prognostic models were evaluated: Cox proportional hazards regression modeling, single-tree recursive partitioning, random survival forest, conditional random forest. Median overall survival from progression was 7.6 months (mean, 10.1; range, 0-86) and 8.0 months (mean, 8.5; range, 0-56) in the training and validation sets, respectively (p = 0.900). Using the Cox model in the training set, independent predictors of poorer overall survival from progression included increasing age at histopathological diagnosis (aHR, 1.47; 95% CI [1.03-2.08]; p = 0.032), RTOG-RPA V-VI classes (aHR, 1.38; 95% CI [1.11-1.73]; p = 0.004), decreasing KPS at progression (aHR, 3.46; 95% CI [2.10-5.72]; p < 0.001), while independent predictors of longer overall survival from progression included surgical resection (aHR, 0.57; 95% CI [0.44-0.73]; p < 0.001) and chemotherapy (aHR, 0.41; 95% CI [0.31-0.55]; p < 0.001). Single-tree recursive partitioning identified KPS at progression, surgical resection at progression, chemotherapy at progression, and RTOG-RPA class at histopathological diagnosis, as main survival predictors in the training set, yielding four risk categories highly predictive of overall survival from progression both in training (p < 0.0001) and validation (p < 0.0001) sets. Both random forest approaches identified KPS at progression as the most important survival predictor. Age, KPS at progression, RTOG-RPA classes, surgical resection at progression and chemotherapy at progression are prognostic for survival in recurrent glioblastomas and should inform the treatment decisions.

Purpose: CD90 (Thy-1) is a glycophosphatidylinositol-anchored glycoprotein considered as a surrogate marker for a variety of stem cells, including glioblastoma (GBM) stem cells (GSC). However, the molecular and cellular functions of CD90 remain unclear. Experimental Design: The function of CD90 in GBM was addressed using cellular models from immortalized and primary GBM lines, in vivo orthotopic mouse models, and GBM specimens' transcriptome associated with MRI features from GBM patients. CD90 expression was silenced in U251 and GBM primary cells and complemented in CD90-negative U87 cells. Results: We showed that CD90 is not only expressed on GSCs but also on more differentiated GBM cancer cells. In GBM patients, CD90 expression was associated with an adhesion/migration gene signature and with invasive tumor features. Modulation of CD90 expression in GBM cells dramatically affected their adhesion and migration properties. Moreover, orthotopic xenografts revealed that CD90 expression induced invasive phenotypes in vivo Indeed, CD90 expression led to enhanced SRC and FAK signaling in our GBM cellular models and GBM patients' specimens. Pharmacologic inhibition of these signaling nodes blunted adhesion and migration in CD90-positive cells. Remarkably, dasatinib blunted CD90-dependent GBM cell invasion in vivo and killed CD90 high primary GSC lines. Conclusions: Our data demonstrate that CD90 is an actor of GBM invasiveness through SRC-dependent mechanisms and could be used as a predictive factor for dasatinib response in CD90 high GBM patients. Clin Cancer Res; 23(23); 7360-74. ©2017 AACR ., (©2017 American Association for Cancer Research.)

A growing literature supports maximal safe resection followed by standard combined chemoradiotherapy (i.e. maximal first-line therapy) for selected elderly glioblastoma patients. To assess the prognostic factors from recurrence in elderly glioblastoma patients treated by maximal safe resection followed by standard combined chemoradiotherapy as first-line therapy. Multicentric retrospective analysis comparing the prognosis and optimal oncological management of recurrent glioblastomas between 660 adult patients aged of < 70 years (standard group) and 117 patients aged of ≥70 years (elderly group) harboring a supratentorial glioblastoma treated by maximal first-line therapy. From recurrence, both groups did not significantly differ regarding Karnofsky performance status (KPS) (p = 0.482). Oncological treatments from recurrence significantly differed: patients of the elderly group received less frequently oncological treatment from recurrence (p < 0.001), including surgical resection (p < 0.001), Bevacizumab therapy (p < 0.001), and second line chemotherapy other than Temozolomide (p < 0.001). In multivariate analysis, Age ≥70 years was not an independent predictor of overall survival from recurrence (p = 0.602), RTOG-RPA classes 5-6 (p = 0.050) and KPS at recurrence <70 (p < 0.001), available in all cases, were independent significant predictors of shorter overall survival from recurrence. Initial removal of ≥ 90% of enhancing tumor (p = 0.004), initial completion of the standard combined chemoradiotherapy (p = 0.007), oncological treatment from recurrence (p < 0.001), and particularly surgical resection (p < 0.001), Temozolomide (p = 0.046), and Bevacizumab therapy (p = 0.041) were all significant independent predictors of longer overall survival from recurrence. Elderly patients had substandard care from recurrence whereas age did not impact overall survival from recurrence contrary to KPS at recurrence <70. Treatment options from recurrence should include repeat surgery, second line chemotherapy and anti-angiogenic agents.

Background: Chronic subdural hematoma (CSDH) is a common neurological pathology, especially in older patients. The actual "gold standard" of treatment is surgical evacuation, with various techniques used across neurosurgical teams. Over the years, there has been growing evidence that inflammatory processes play a major role in the pathogenesis of CSDH. In that context, the use of corticosteroids has been proposed alone or as an adjuvant treatment to surgery. However, this practice remains very empirical and there is a need for high-quality-of-evidence studies to clarify the role of corticosteroids in the management of CSDH., Methods/design: We propose a double-blind, randomized controlled trial comparing methylprednisolone versus placebo in the treatment of CSDH without clinical and/or radiological signs of severity. The treatment will be administered daily for a duration of 3 weeks, at a dose of 1 mg/kg. The primary endpoint will be the delay of occurrence of surgical treatment at 1 month following the introduction of the treatment. Secondary endpoints will include the rate of recourse to surgery, survival rate, quality of life and functional assessments, occurrence of systemic secondary effects and radiological assessment of the response to treatment. This multimodal assessment will be done at 1, 3 and 6 months. Two hundred and two patients (101 per arm) are expected to be included considering our primary hypotheses., Discussion: This trial started in June 2016; its results may open interesting alternatives to surgery in the management of patients harboring a CSDH, and may provide insights into the natural history of this common pathology., Trial Registration: ClinicalTrials.gov, ID: NCT02650609 . Registered on 4 January 2016. Graphical output of the OBF boundaries.

Background: Anaplastic gangliogliomas (GGGs) are rare tumors whose natural history is poorly documented. We aimed to define their clinical and imaging features and to identify prognostic factors., Methods: Consecutive cases of anaplastic GGGs in adults prospectively entered into the French Brain Tumor Database between March 2004 and April 2014 were screened. After diagnosis was confirmed by pathological review, clinical, imaging, therapeutic, and outcome data were collected retrospectively., Results: Forty-three patients with anaplastic GGG (median age, 49.4 y) from 18 centers were included. Presenting symptoms were neurological deficit (37.2%), epileptic seizure (37.2%), or increased intracranial pressure (25.6%). Typical imaging findings were unifocal location (94.7%), contrast enhancement (88.1%), central necrosis (43.2%), and mass effect (47.6%). Therapeutic strategy included surgical resection (95.3%), adjuvant radiochemotherapy (48.8%), or radiotherapy alone (27.9%). Median progression-free survival (PFS) and overall survival (OS) were 8.0 and 24.7 months, respectively. Three- and 5-year tumor recurrence rates were 69% and 100%, respectively. The 5-year survival rate was 24.9%. Considering unadjusted significant prognostic factors, tumor midline crossing and frontal location were associated with shorter OS. Temporal and parietal locations were associated with longer and shorter PFS, respectively. None of these factors remained statistically significant in multivariate analysis., Conclusions: We report a large series providing clinical, imaging, therapeutic, and prognostic features of adult patients treated for an intracerebral anaplastic GGG. Our results show that pathological diagnosis is difficult, that survivals are only slightly better than for glioblastomas, and that complete surgical resection followed with adjuvant chemoradiotherapy offers longer survival., (© The Author(s) 2016. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com)

Cellular stress induced by the accumulation of misfolded proteins at the endoplasmic reticulum (ER) is a central feature of secretory cells and is observed in many tissues in various diseases, including cancer, diabetes, obesity, and neurodegenerative disorders. Cellular adaptation to ER stress is achieved by the activation of the unfolded protein response (UPR), an integrated signal transduction pathway that transmits information about the protein folding status at the ER to the cytosol and nucleus to restore proteostasis. In the past decade, ER stress has emerged as a major pathway in remodeling gene expression programs that either prevent transformation or provide selective advantage in cancer cells. Controlled by the formation of a dynamic scaffold onto which many regulatory components assemble, UPR signaling is a highly regulated process that leads to an integrated reprogramming of the cell. In this Review, we provide an overview of the regulatory mechanisms underlying UPR signaling and how this pathway modulates cancer progression, particularly the aggressiveness and chemotherapeutic resistance exhibited by glioblastoma, a form of brain cancer. We also discuss the emerging cross-talk between the UPR and related metabolic processes to ensure maintenance of proteostasis, and we highlight possible therapeutic opportunities for targeting the pathway with small molecules., (Copyright © 2017, American Association for the Advancement of Science.)

Purpose: The aim of this study was to assess the interbody fusion rate for patients treated by anterior cervical interbody fusion (ACIF) using polyetheretherketone (PEEK) cages filled with synthetic bone graft in acute cervical spine injury., Materials and Methods: Twenty-nine patients (mean age: 49 years) with monosegmental instability due to cervical spine injury were followed. We assessed the rate of and time to interbody fusion at 1-year follow-up. In case of secondary displacement, we analysed its causes and surgical management., Results: The rate of fusion was 86.2%. The mean time to fusion was 7.2 months. Interbody fusion was observed at 3 months in 4 patients, at 6 months in 14 and at 1 year in 7. Four patients had secondary displacement within 3 months., Conclusion: ACIF with a PEEK cage filled with synthetic bone graft seems to be an alternative to iliac crest bone graft with no morbidity related to the harvest site., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

Background: Susceptibility-weighted imaging (SWI) of brain tumors provides information about neoplastic vasculature and intratumoral micro- and macrobleedings. Low- and high-grade gliomas can be distinguished by SWI due to their different vascular characteristics. Fractal analysis allows for quantification of these radiological differences by a computer-based morphological assessment of SWI patterns., Objective: To show the feasibility of SWI analysis on 3-T magnetic resonance imaging to distinguish different kinds of brain tumors., Methods: Seventy-eight patients affected by brain tumors of different histopathology (low- and high-grade gliomas, metastases, meningiomas, lymphomas) were included. All patients underwent preoperative 3-T magnetic resonance imaging including SWI, on which the lesions were contoured. The images underwent automated computation, extracting 2 quantitative parameters: the volume fraction of SWI signals within the tumors (signal ratio) and the morphological self-similar features (fractal dimension [FD]). The results were then correlated with each histopathological type of tumor., Results: Signal ratio and FD were able to differentiate low-grade gliomas from grade III and IV gliomas, metastases, and meningiomas (P < .05). FD was statistically different between lymphomas and high-grade gliomas (P < .05). A receiver-operating characteristic analysis showed that the optimal cutoff value for differentiating low- from high-grade gliomas was 1.75 for FD (sensitivity, 81%; specificity, 89%) and 0.03 for signal ratio (sensitivity, 80%; specificity, 86%)., Conclusion: FD of SWI on 3-T magnetic resonance imaging is a novel image biomarker for glioma grading and brain tumor characterization. Computational models offer promising results that may improve diagnosis and open perspectives in the radiological assessment of brain tumors., Abbreviations: FD, fractal dimensionSR, signal ratioSWI, susceptibility-weighted imaging.

The Unfolded Protein Response (UPR) is an adaptive cellular program used by eukaryotic cells to cope with protein misfolding stress in the Endoplasmic Reticulum (ER). During tumor development, cancer cells are facing intrinsic (oncogene activation) and extrinsic (limiting nutrient or oxygen supply; exposure to chemotherapies) challenges, with which they must cope to survive. Primary brain tumors are relatively rare but deadly and present a significant challenge in the determination of risk factors in the population. These tumors are inherently difficult to cure because of their protected location in the brain. As such surgery, radiation and chemotherapy options carry potentially lasting patient morbidity and incomplete tumor cure. Some of these tumors, such as glioblastoma, were reported to present features of ER stress and to depend on UPR activation to sustain growth, but to date there is no clear general representation of the ER stress status in primary brain tumors. In this review, we describe the key molecular mechanisms controlling the UPR and their implication in cancers. Then we extensively review the literature reporting the status of ER stress in various primary brain tumors and discuss the potential impact of such observation on patient stratification and on the possibility of developing appropriate targeted therapies using the UPR as therapeutic target. This article is part of a Special Issue entitled SI:ER stress., (Copyright © 2016 Elsevier B.V. All rights reserved.)

The aims of this multicentre retrospective study were to identify prognostic or therapeutic factors impacting on overall survival in patients with gliosarcoma. The analysis included all patients treated for gliosarcoma between 1998 and 2014 in seven French academic centres. Seventy-five patients with a median age of 60 years (range from 23 to 79 years) were treated with a combination of surgery (n = 66), radiotherapy (adjuvant for 64 patients and exclusive for 8 patients) and temozolomide based chemotherapy (n = 58). Median follow-up was 12 months (range from 2 to 71 months). Two-year overall survival (OS) and disease free survival rates were 12 % (95 % CI 4-20 %) and 2 % (95 % CI 0-6 %), respectively. The median OS was 13 months. Treatment at recurrence consisted of chemotherapy (n = 38) (bevazicumab for 18 patients, repeat temozolomide for 10 patients), salvage surgery (n = 8) and radiochemotherapy (n = 1). In univariate analysis, younger age, higher total dose of radiotherapy, longer time to recurrence and treatment at recurrence significantly increased OS. In multivariate analysis, high total dose of radiotherapy (HR = 0.97, p = 0.007) and treatment at recurrence (HR = 0.28, p < 0.001) were favourable prognostic factors of OS. Radiotherapy at a minimum dose of 54 Gy and salvage treatment increased OS of gliosarcoma. Unlike glioblastoma, in our analysis, TMZ based chemotherapy was not associated with an improvement in OS compared to patients who received radiation therapy only.

Purpose: The dorsolateral prefrontal cortex (DLPFC) is a cortical area involved in higher cognitive functions, and at the center of the pathophysiology of mental disorders such as depression and schizophrenia. Considering these major roles and the development of deep brain stimulation, the object of this study was to assess the patterns of connectivity of the DLPFC with its main subcortical relay, the thalamus, with the help of probabilistic tractography., Methods: We used T1-weighted imaging and diffusion data from 18 subjects from the Human Connectome Project. The DLPFC and the thalamic nuclear groups were defined using the combination of atlases, sulcogyral anatomy and cytoarchitectonic data. Probabilistic tractography was performed from the DLPFC to the thalamus. The patterns of connectivity were assessed using two indexes: (1) a connectivity index (CI) which evaluate the strength of connection (2) an asymmetry index (AI) which explores the inter-hemispheric variability., Results: The analysis of CI showed significant connections between the DLPFC and the dorsomedial nuclei (p < 0.05), the anterior nuclear groups (p < 0.05) and the right centromedian nucleus (p < 0.05). No link was found between handedness and AI (p > 0.05). Most of subjects (15/18) had a right predominance of the thalamo cortical connections of the DLPFC., Conclusions: Probabilistic tractography appears as a valuable non-invasive tool for the exploration of the thalamocortical connections between the dorsolateral prefrontal cortex and thalamic nuclei. It allowed to show different inter-hemispheric patterns of connectivity, and highlighted the centromedian nucleus as a key subcortical relay of executive functions.

The Unfolded Protein Response (UPR) is an adaptive cellular program used by eukaryotic cells to cope with protein misfolding stress in the Endoplasmic Reticulum (ER). During tumor development, cancer cells are facing intrinsic (oncogene activation) and extrinsic (limiting nutrient or oxygen supply; exposure to chemotherapies) challenges, with which they must cope to survive. Primary brain tumors are relatively rare but deadly and present a significant challenge in the determination of risk factors in the population. These tumors are inherently difficult to cure because of their protected location in the brain. As such surgery, radiation and chemotherapy options carry potentially lasting patient morbidity and incomplete tumor cure. Some of these tumors, such as glioblastoma, were reported to present features of ER stress and to depend on UPR activation to sustain growth, but to date there is no clear general representation of the ER stress status in primary brain tumors. In this review, we describe the key molecular mechanisms controlling the UPR and their implication in cancers. Then we extensively review the literature reporting the status of ER stress in various primary brain tumors and discuss the potential impact of such observation on patient stratification and on the possibility of developing appropriate targeted therapies using the UPR as therapeutic target., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Background: To assess the influence of the time interval between surgical resection and standard combined chemoradiotherapy on survival in newly diagnosed and homogeneously treated (surgical resection plus standard combined chemoradiotherapy) glioblastoma patients; while controlling confounding factors (extent of resection, carmustine wafer implantation, functional status, neurological deficit, and postoperative complications)., Methods: From 2005 to 2011, 692 adult patients (434 men; mean of 57.5 ± 10.8 years) with a newly diagnosed glioblastoma were enrolled in this retrospective multicentric study. All patients were treated by surgical resection (65.5% total/subtotal resection, 34.5% partial resection; 36.7% carmustine wafer implantation) followed by standard combined chemoradiotherapy (radiotherapy at a median dose of 60 Gy, with daily concomitant and adjuvant temozolomide). Time interval to standard combined chemoradiotherapy was analyzed as a continuous variable and as a dichotomized variable using median and quartiles thresholds. Multivariate analyses using Cox modeling were conducted., Results: The median progression-free survival was 10.3 months (95% CI, 10.0-11.0). The median overall survival was 19.7 months (95% CI, 18.5-21.0). The median time to initiation of combined chemoradiotherapy was 1.5 months (25% quartile, 1.0; 75% quartile, 2.2; range, 0.1-9.0). On univariate and multivariate analyses, OS and PFS were not significantly influenced by time intervals to adjuvant treatments. On multivariate analysis, female gender, total/subtotal resection and RTOG-RPA classes 3 and 4 were significant independent predictors of improved OS., Conclusions: Delaying standard combined chemoradiotherapy following surgical resection of newly diagnosed glioblastoma in adult patients does not impact survival., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Background: The standard of care for newly diagnosed glioblastoma is maximal safe surgical resection, followed by chemoradiation therapy. We assessed carmustine wafer implantation efficacy and safety when used in combination with standard care., Methods: Included were adult patients with (n = 354, implantation group) and without (n = 433, standard group) carmustine wafer implantation during first surgical resection followed by chemoradiation standard protocol. Multivariate and case-matched analyses (controlled propensity-matched cohort, 262 pairs of patients) were conducted., Results: The median progression-free survival was 12.0 months (95% CI: 10.7-12.6) in the implantation group and 10.0 months (9.0-10.0) in the standard group and the median overall survival was 20.4 months (19.0-22.7) and 18.0 months (17.0-19.0), respectively. Carmustine wafer implantation was independently associated with longer progression-free survival in patients with subtotal/total surgical resection in the whole series (adjusted hazard ratio [HR], 0.76 [95% CI: 0.63-0.92], P = .005) and after propensity matching (HR, 0.74 [95% CI: 0.60-0.92], P = .008), whereas no significant difference was found for overall survival (HR, 0.95 [0.80-1.13], P = .574; HR, 1.06 [0.87-1.29], P = .561, respectively). Surgical resection at progression whether alone or combined with carmustine wafer implantation was independently associated with longer overall survival in the whole series (HR, 0.58 [0.44-0.76], P < .0001; HR, 0.54 [0.41-0.70], P < .0001, respectively) and after propensity matching (HR, 0.56 [95% CI: 0.40-0.78], P < .0001; HR, 0.46 [95% CI: 0.33-0.64], P < .0001, respectively). The higher postoperative infection rate in the implantation group did not affect survival., Conclusions: Carmustine wafer implantation during surgical resection followed by the standard chemoradiation protocol for newly diagnosed glioblastoma in adults resulted in a significant progression-free survival benefit., (© The Author(s) 2015. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: The expansion of endovascular techniques for intracranial aneurysms has led to a global decrease in vascular neurosurgery activity. This situation might impact neurosurgeons' level of expertise, even though they all might have to deal with this surgically challenging pathology. In that context, we wanted to assess the impact of cumulative surgical experience on the outcome of patients with poor-grade subarachnoid haemorrhage (SAH) and intracerebral haemorrhage (ICH) treated by microsurgery., Methods: Sixty-seven patients who underwent surgery for a ruptured aneurysm with SAH and ICH, and a WFNS scale of IV/V, were included. Surgeries were performed by five surgeons, whose experience was judged by the total number of aneurysm surgeries performed. The outcome was assessed by three indicators: intraoperative rupture (IOR), early mortality, and the modified Rankin Scale at last follow-up. The time of IOR was reported on an IOR score. The correlation between surgical experience and outcome was assessed by linear regression. Nonlinear regression was used to assess the correlation of the data with a learning curve model., Results: The analysis showed an influence of surgical experience on intraoperative rupture, with no effect on long-term outcome. No influence was found on early mortality. Increased surgical experience seems to reduce IOR during aneurysm dissection and clip repositioning. Intraoperative rupture data fit Wright's learning curve model., Conclusion: This study suggests a direct impact of cumulative experience on the course of ruptured aneurysm surgery and pleads for the use of training and simulation programmes dedicated to neurovascular surgery.

Primary cell lines derived as neurospheres, enriched in cancer stem cells, are currently the focus of interest in glioblastoma to test new drugs, because of their tumor initiating abilities and resistance to conventional therapies. However, not all glioblastoma samples are propagatable under neurosphere culture and not all neurosphere cell lines are tumorigenic. These cells therefore cannot recapitulate the heterogeneity of glioblastoma samples. We have conducted a proteomic analysis of primary glioblastoma cell lines derived either as adherent cells in the presence of serum (n=11) or as neurospheres (n=12). A total of 963 proteins were identified by nano-LC/Q-TOF MS: 342 proteins were found only in neurosphere lines and were mostly implicated in various metabolic and cellular processes, while 112 proteins were found only in adherent cells and mostly linked to cell adhesion. A protein signature of 10 proteins, 9 of them involved in a cell adhesion pathway, characterized adherent lines. Neurospheres were characterized by 73 proteins mostly linked to DNA metabolic processes associated to cell cycle and protein metabolism. In the Repository of Molecular Brain Neoplasia Data, expression of genes coding for several proteins related to adherent cells or neurospheres were of prognostic relevance for glioblastoma., Biological Significance: Primary cell lines enriched in cancer stem cells (CSC) have become popular models for testing new drugs for glioblastoma. In this proteomic study on an important number of cell lines obtained either as adherent cells in the presence of serum (a classic way to derive cell lines) or as neurospheres (enriched in CSC), we show that each type of cell line displays different GBM-specific features, highlighting that these two culture types are complementary tools for drug screening., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Purpose: Non-traumatic cervical chronic joint instability in young adults is a rare and underexplored entity. We assessed the diagnostic relevance of dynamic MRI, and the clinical and radiological outcome after anterior cervical interbody fusion (ACIF) in these cases., Methods: Six young patients (mean age 34 years) with cervical myelopathy without compression on static imaging had a dynamic MRI. Joint instability was defined by a reduction of the canal diameter on dynamic sequences. Clinical and radiological outcomes were assessed after surgery by examination, cervical X-rays, static and dynamic MRI., Results: All the patients had joint instability. Four patients underwent surgery. Clinical status improved 1 year after surgery. All patients had a satisfactory fusion at 6-month follow-up and no residual compression at 1 year., Conclusion: Dynamic MRI can help detect a joint instability in young patients with cervical myelopathy without compression. ACIF seems to be efficient in these cases.

Background: Haemangioblastomas are benign vascular tumours that may appear sporadically or in von Hippel-Lindau disease. Despite their higher incidence, sporadic haemangioblastomas have been less studied than syndromic ones. In this article, we evaluate the specific features, outcome and quality of life of patients with intracranial sporadic haemangioblastomas (ISHs) operated on in our institution., Methods: Between 1998 and 2010, 38 patients harbouring 38 ISHs were operated on in our department. Their clinical, biological, radiological and surgical features were retrospectively reviewed. All patients were contacted for a quality-of-life (QOL) survey assessed by the Short Form 36 questionnaire (SF36). The mean duration of follow-up was 40 months (13-108 months)., Results: ISH represented 0.9 % of primary intracranial neoplasms treated in our centre during this period. Patients comprised 23 men and 15 women with a mean age of 47 years. None had polycythaemia. Cerebellar locations accounted for 79 % of ISHs, and brainstem ISH with involvement of the floor of the fourth ventricle represented 11 % of ISHs. At last follow-up, two patients harbouring solid medulla oblongata haemangioblastoma had died following severe bulbar syndrome and five patients had died of unrelated causes. One patient had multiple surgeries for three recurrences. Tumoral control was achieved in all cases at last follow-up. Results of the SF-36 questionnaire were as follows: median physical functioning score 100 (range 0-100), median physical problems score 100 (range 0-100), median bodily pain score 100 (range 45-100), median social functioning score 100 (range 25-100), median general mental health score 84 (range 40-92), median emotional problems score 100 (range 0-100), median vitality score 70 (range 35-80) and median general health perceptions score 70 (range 35-100). Mean QOL scores were similar to the general healthy population., Conclusion: Surgery of ISH provides good QOL and tumoral control except for those located in the medulla oblongata. We recommend considering a careful multimodal therapeutic approach, including radiosurgery for these specific locations.

In this chapter, we report the results of orbital tumor management in a few neurosurgical departments and compare it to a Paris neurosurgical department that has developed a close relation with an ophthalmological department. These departments' activity is quite low, treating mainly sphenoorbital meningiomas. Other tumor groups are unequally and sporadically managed., (Copyright 2010 Elsevier Masson SAS. All rights reserved.)