Search

The NA62 experiment at CERN, configured in beam-dump mode, has searched for dark photon decays in flight to electron-positron pairs using a sample of 1.4×10^{17} protons on dump collected in 2021. No evidence for a dark photon signal is observed. The combined result for dark photon searches in lepton-antilepton final states is presented and a region of the parameter space is excluded at 90% confidence level, improving on previous experimental limits for dark photon mass values between 50 and 600  MeV/c^{2} and coupling values in the range 10^{-6} to 4×10^{-5}. An interpretation of the e^{+}e^{-} search result in terms of the emission and decay of an axionlike particle is also presented.

Cortical malformations such as focal cortical dysplasia type II (FCDII) are associated with pediatric drug-resistant epilepsy that necessitates neurosurgery. FCDII results from somatic mosaicism due to post-zygotic mutations in genes of the PI3K-AKT-mTOR pathway, which produce a subset of dysmorphic cells clustered within healthy brain tissue. Here we show a correlation between epileptiform activity in acute cortical slices obtained from human surgical FCDII brain tissues and the density of dysmorphic neurons. We uncovered multiple signatures of cellular senescence in these pathological cells, including p53/p16 expression, SASP expression and senescence-associated β-galactosidase activity. We also show that administration of senolytic drugs (dasatinib/quercetin) decreases the load of senescent cells and reduces seizure frequency in an Mtor S2215F FCDII preclinical mouse model, providing proof of concept that senotherapy may be a useful approach to control seizures. These findings pave the way for therapeutic strategies selectively targeting mutated senescent cells in FCDII brain tissue., (© 2024. The Author(s).)

Abstract: This study aimed to characterize the sensory responses observed when electrically stimulating the white matter surrounding the posterior insula and medial operculum (PIMO). We reviewed patients operated on under awake conditions for a glioma located in the temporoparietal junction. Patients' perceptions were retrieved from operative reports. Stimulation points were registered in the Montreal Neurological Institute template. A total of 12 stimulation points in 8 patients were analyzed. Painful sensations in the contralateral leg were reported (5 sites in 5 patients) when stimulating the white matter close to the parcel OP2/3 of the Glasser atlas. Pain had diverse qualities: burning, tingling, crushing, or electric shock. More laterally, in the white matter of OP1, pain and heat sensations in the upper part of the body were described (5 sites in 2 patients). Intermingled with these sites, vibration sensations were also reported (3 sites in 2 patients). Based on the tractograms of 44 subjects from the Human Connectome Project data set, we built a template of the pathways linking the thalamus to OP2/3 and OP1. Pain sites were located in the thalamo-OP2/3 and thalamo-OP1 tracts. Heat sites were located in the thalamo-OP1 tract. In the 227 awake surgeries performed for a tumor located outside of the PIMO region, no patients ever reported pain or heat sensations when stimulating the white matter. Thus, we propose that the thalamo-PIMO connections constitute the main cortical inputs for nociception and thermoception and emphasize that preserving these fibers is of utmost importance to prevent the postoperative onset of a debilitating insulo-opercular pain syndrome., (Copyright © 2023 International Association for the Study of Pain.)

Objective: To describe pure insular ictal semiology and patterns of extra-insular spread demonstrated by stereoelectroencephalography (SEEG) according to a classification based on the insular cytoarchitecture., Methods: We investigated the ictal semiology in 17 patients undergoing SEEG for insular epilepsy. The insular cortex was divided into three regions roughly overlapping with the agranular, dysgranular and granular regions. Ictal semiology was described accordingly: anterior insula (AI, short anterior and middle gyri), middle insula (MI, short posterior and long anterior gyri) and posterior insula (PI, long posterior gyrus)., Results: Awareness impairment occurred secondarily to extra-insular ictal spread. Subjective manifestations were constant. AI seizures (n = 3) presented with autonomic (increased heart rate [HR], respiratory changes), oropharyngeal (mainly throat sensations), emotional (fear, anguish) semiology and the "hand-to-throat" sign followed by frontal-like semiology. MI seizures (n = 8) presented with mainly non-painful paresthesia, some autonomic (respiratory, increased HR), oropharyngeal or thermic symptoms and early motor features with spread to the opercular cortex. PI seizures (n = 6) were characterized by somatosensory semiology, mainly paresthesia potentially painful, and cephalic sensations., Conclusions: Cytoarchitectonic-based classification and the corresponding ictal features support the antero-posterior grading of insular seizures and highlight specific ictal symptoms., Significance: This refinement of insular semiology can help optimize the planning of SEEG for presumed insular epilepsy., (Copyright © 2023 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Background: Transorbital endoscopic approaches have been described for pathologies of anterior and middle fossae. Standard lateral orbitotomy gives access to mesial temporal lobe, but the axis of work is partially obscured by the temporal pole and working corridor is limited., Objective: To evaluate the usefulness of an inferolateral orbitotomy to provide a more direct corridor to perform a transuncal selective amygdalohippocampectomy., Methods: Three adult cadaveric specimens were used for a total of 6 dissections. A step-by-step description and illustration of the transuncal corridor for a selective amygdalohippocampectomy were performed using the inferolateral orbitotomy through an inferior eyelid conjunctival incision. The anatomic landmarks were demonstrated in detail. Orbitotomies and angles of work were measured from computed tomography scans, and the area of resection was illustrated by postdissection MRI., Results: Inferior eyelid conjunctival incision was made for exposure of the inferior orbital rim. Inferolateral transorbital approach was performed to access the transuncal corridor. Endoscopic selective amygdalohippocampectomy was performed through the entorhinal cortex without damage to the temporal neocortex or Meyer's loop. The mean horizontal diameter of the osteotomy was 14.4 mm, and the vertical one was 13.6 mm. The mean angles of work were 65° and 35.5° in the axial and sagittal planes, respectively. Complete amygdalohippocampectomy was achieved in all 6 dissections., Conclusion: Transuncal selective amygdalohippocampectomy was feasible in cadaveric specimens using the inferolateral transorbital endoscopic approach avoiding damage to the temporal neocortex and Meyer's loop. The inferior eyelid conjunctival incision may result in an excellent cosmetic outcome., (Copyright © Congress of Neurological Surgeons 2023. All rights reserved.)

Background: Delayed return of gastrointestinal function (DGIF) after hepatectomy can involve increased morbidity and prolonged hospital stay. Yet, data on incidence and risks factors are lacking., Methods: All consecutive patients who underwent hepatectomy between June 2018 and December 2020 were included. All patients were included in an enhanced recovery after surgery (ERAS) program. DGIF was defined by the need for nasogastric tube (NGT) insertion after surgery. DGIF risk factors were identified., Results: Overall, 206 patients underwent hepatectomy. DGIF occurred in 41 patients (19.9%) after a median time of 2 days (range, 1-14). Among them, 6 patients (14.6%) developed aspiration pneumonia, of which one required ICU for mechanical ventilation. DGIF developed along with an intraabdominal complication in 7 patients (biliary fistula, n = 5; anastomotic fistula, n = 1; adhesive small bowel obstruction, n = 1). DGIF was associated with significantly increased severe morbidity rate (p = 0.001), prolonged time to normal food intake (p < 0.001) and hospital stay (p < 0.001) and significantly decreased overall compliance rate (p = 0.001). Independent risk factors of DGIF were age (p < 0.001), vascular reconstruction (p = 0.007), anaesthetic induction using volatiles (p = 0.003) and epidural analgesia (p = 0.004). Using these 4 variables, a simple DGIF risk score has been developed allowing patient stratification in low-, intermediate- and high-risk groups., Conclusion: DGIF after hepatectomy was frequently observed and significantly impacted postoperative outcomes. Identifying risk factors remains critical for preventing its occurrence., (Copyright © 2022 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Background and Objectives: Focal cortical dysplasia type 2 (FCD 2 ) in the central region can cause drug-resistant epilepsy for which surgery remains challenging because of subsequent functional deficits. Advances in imaging and surgical techniques have progressively improved outcome. We aimed to assess the benefits on epilepsy and the functional risks after FCD 2 resections in these highly eloquent areas., Methods: We retrospectively studied all consecutive patients with histologically confirmed FCD 2 located in the central region operated on between 2000 and 2019 at a single center. We analyzed electroclinical and imaging features (including fMRI), seizure outcome, and early and late postoperative neurologic status correlating to anatomo-functional areas (primary motor cortex [PMC], paracentral lobule [PCL], supplementary motor area [SMA], precentral gyrus [PrCG], postcentral gyrus [PoCG], central operculum [COp])., Results: Sixty patients (35 female, age 7-65 years) were included in the study. Epilepsy was characterized by early onset, high seizure frequency with clusters (30-90/d), drop attacks, and status epilepticus. Ictal semiology included sensory-motor auras, motor and postural manifestations, and postictal motor deficits. EEG and stereo-EEG patterns were like those typically recorded in FCD 2 . MRI was positive in 63% and 18 F-fluorodeoxyglucose-PET was positive in 86% of the patients. fMRI demonstrated activations close to the FCD 2 (59%) or minor reorganization (41%) but none within the lesion. Seizure-free outcome (2- to 20-year follow-up) was obtained in 53 patients (88%), including 37 achieving Engel class IA (62%), correlating with complete FCD 2 removal. Early transitory postoperative deficits occurred in 52 patients (87%), which were severe in 19, mostly after PMC, PCL, and SMA resections, while PrCG, PoCG, and COp resections were associated with minor/moderate deficits. Total recovery was observed in 21 of 52 patients (40%), while a permanent deficit (>2 years) persisted in 31 (minor 19, moderate 9, major 3). The best outcome (seizure freedom without deficit [48%] or with minor deficit (28%]) was significantly more frequent in children ( p = 0.025). Antiseizure medications were discontinued in 28 patients (47%). Quality of life correlated with seizure-free outcome and absence of postoperative deficit; 43 patients (72%) reported a schooling or socio-professional improvement., Discussion: Excellent seizure outcome and low rates of major permanent disability can be achieved after central FCD 2 resections despite functional risks., Classification of Evidence: Due to its retrospective nature, this study provides Class IV evidence that good seizure outcomes with minor additional deficits can be achieved after epilepsy surgery in the central region., (© 2022 American Academy of Neurology.)

Nowadays, surgical removal remains the standard method to treat brain tumors. During surgery, the neurosurgeon may encounter difficulties to delimitate tumor boundaries and the infiltrating areas as they have a similar visual appearance to adjacent healthy zones. These infiltrating residuals increase the tumor recurrence risk, which decreases the patient's post-operation survival time. To help neurosurgeons improve the surgical act by accurately delimitating healthy from cancerous areas, our team is developing an intraoperative multimodal imaging tool. It consists of a two-photon fluorescence fibered endomicroscope that is intended to provide a fast, real-time, and reliable diagnosis information. In parallel to the instrumental development, a large optical database is currently under construction in order to characterize healthy and tumor brain tissues with their specific optical signature using multimodal analysis of the endogenous fluorescence. Our previous works show that this multimodal analysis could provide a reliable discrimination response between different tissue types based on several optical indicators. Here, our goal is to show that the two-photon fibered endomicroscope is able to provide, based on the same approved indicators in the tissue database, the same reliable response that could be used intraoperatively. We compared the spectrally resolved and time-resolved fluorescence signal, generated by our two-photon bimodal endoscope from 46 fresh brain tissue samples, with a similar signal provided by a standard reference benchtop multiphoton microscope that has been validated for tissue diagnosis. The higher excitation efficiency and collection ability of an endogenous fluorescence signal were shown for the endoscope setup. Similar molecular ratios and fluorescence lifetime distributions were extracted from the two compared setups. Spectral discrimination ability of the bimodal endoscope was validated. As a preliminary step before tackling multimodality, the ability of the developed bimodal fibered endoscope to excite and to collect efficiently as well as to provide a fast exploitable high-quality signal that is reliable to discriminate different types of human brain tissues was validated., 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 © 2022 Mehidine, Devaux, Varlet and Abi Haidar.)

•The transorbital approach combining eyebrow incision and crescent-shaped craniotomy increases the surgical freedom to access the anterior and middle skull-base.•The technic allows the use of both endoscope and microscope.•The concept is at the crossroad between the supraorbital keyhole and endoscopic trans-orbital approach., (© 2022 Published by Elsevier B.V. on behalf of EUROSPINE, the Spine Society of Europe, EANS, the European Association of Neurosurgical Societies.)

Searches for the lepton number violating K^{+}→π^{-}μ^{+}e^{+} decay and the lepton flavor violating K^{+}→π^{+}μ^{-}e^{+} and π^{0}→μ^{-}e^{+} decays are reported using data collected by the NA62 experiment at CERN in 2017-2018. No evidence for these decays is found and upper limits of the branching ratios are obtained at 90% confidence level: B(K^{+}→π^{-}μ^{+}e^{+})<4.2×10^{-11}, B(K^{+}→π^{+}μ^{-}e^{+})<6.6×10^{-11} and B(π^{0}→μ^{-}e^{+})<3.2×10^{-10}. These results improve by 1 order of magnitude over previous results for these decay modes.

Background: Multiple biopsy samples are warranted for the histomolecular diagnosis of diffuse gliomas in the current molecular era, which possibly increases morbidity., Objective: We assessed diagnostic yield, safety, and risk factors of postoperative morbidity after robot-assisted serial stereotactic biopsy sampling along 1 biopsy trajectory for diffuse gliomas., Methods: Observational retrospective analysis of consecutive magnetic resonance imaging-based robot-assisted stereotactic biopsies performed at a single institution to assess the diagnosis of nonresectable newly diagnosed supratentorial diffuse gliomas in adults (2006-2016)., Results: In 377 patients, 4.2 ± 1.9 biopsy samples were obtained at 2.6 ± 1.2 biopsy sites. The histopathologic diagnosis was obtained in 98.7% of cases. Preoperative neurologic deficit (P = 0.030), biopsy site hemorrhage ≥20 mm (P = 0.004), and increased mass effect on postoperative imaging (P = 0.014) were predictors of a new postoperative neurologic deficit (7.7%). Postoperative neurologic deficit (P < 0.001) and increased mass effect on postoperative imaging (P = 0.014) were predictors of a Karnofsky Performance Status decrease ≥20 points postoperatively (4.0%). Increased intracranial pressure preoperatively (P = 0.048) and volume of the contrast-enhanced area ≥13 cm 3 (P = 0.048) were predictors of an increased mass effect on postoperative imaging (4.4%). Preoperative Karnofsky Performance Status <70 (P = 0.045) and increased mass effect on postoperative imaging (P < 0.001) were predictors of mortality 1 month postoperatively (2.9%). Preoperative neurologic deficit (P = 0.005), preoperative Karnofsky Performance Status <70 (P < 0.001), subventricular zone contact (P = 0.004), contrast enhancement (P = 0.018), and steroid use (P = 0.003), were predictors of the inability to discharge to home postoperatively (37.0%)., Conclusions: Robot-assisted stereotactic biopsy sampling results in high diagnostic accuracy with low complication rates. Multiple biopsy sites and samples do not increase postoperative complications., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Postoperative intracerebral haematomas represent a serious complication following stereotactic biopsy. We investigated the possible underlying causes - poor planning or poor execution - of postoperative intracerebral haematomas following stereotactic biopsies., Methods: We performed a technical investigation using a retrospective single-centre consecutive series of robot-assisted stereotactic biopsies for a supratentorial diffuse glioma in adults. Each actual biopsy trajectory was reviewed to search for a conflict with an anatomical structure at risk., Results: From 379 patients, 12 (3.2%) presented with a postoperative intracerebral haematoma ≥20 mm on postoperative CT-scan (3 requiring surgical evacuation); 11 of them had available intraoperative imaging (bi-planar stereoscopic teleangiography x-rays at each biopsy site). The actual biopsy trajectory was similar to the planned biopsy trajectory in these 11 cases. In 72.7% (8/11) of these cases, the actual biopsy trajectory was found to contact a structure at risk (blood vessel and cerebral sulcus) and identified as the intracerebral haematoma origin., Conclusions: Robot-assisted stereotactic biopsy is an accurate procedure. Postoperative intracerebral haematomas mainly derive from human-related errors during trajectory planning., (© 2021 John Wiley & Sons Ltd.)

Meningioma is the most common primary intracranial extra-axial tumor. Total surgical removal is the standard therapeutic method to treat this type of brain tumors. However, the risk of recurrence depends on the tumor grade and the extent of the resection including the infiltrated dura mater and, if necessary, the infiltrated bone. Therefore, proper resection of all invasive tumor borders without touching eloquent areas is of primordial in order to decrease the risk of recurrence. Nowadays, none of the intraoperative used tools is able to provide a precise real-time histopathological information on the tumor surrounding areas to help the surgeon to achieve a gross total removal. To respond to this problem, our team is developing a multimodal two-photon fluorescence endomicroscope, compatible with the surgeon tool, to better delimitate tumor boundaries, relying on the endogenous fluorescence of brain tissues. In this context, we are building a tissue database in order to specify each brain tissue, whether healthy or tumoral, with its specific optical signature. In this study, we present a multimodal and multiscale optical measurements on non-tumoral control brain tissue obtained in epilepsy surgery patients and several meningioma grades. We investigated tissue auto-fluorescence to track the molecular changes associated with the tumor grade from deep ultra-violet (DUV) to near infrared (NIR) excitation. Micro-spectroscopy, fluorescence lifetime imaging, two-photon fluorescence imaging and Second Harmonic Generation (SHG) imaging were performed. Several optically derived parameters such as collagen crosslinks fluorescence in DUV, SHG emission in NIR and long lifetime intensity fraction of Nicotinamide Adenine Dinucleotide and Flavins were correlated to discriminate cancerous tissue from control one. While collagen response managed to discriminate meningioma grades from control samples with a 100% sensitivity and 90% specificity through a 3D discriminative algorithm.

Objective: Takayasu arteritis (TAK) is a large vessel vasculitis affecting young women of childbearing age. The outcome of pregnancies in TAK patients, factors associated with maternal and foetal complications and adverse outcomes were analysed., Methods: All pregnancies in women with a TAK diagnosis were retrospectively included from 20 French hospitals providing care for TAK, until August 2015., Results: The study consisted of 43 pregnancies in 33 women, including 29 with a pre-existing TAK diagnosis and 4 diagnosed during pregnancy. Complications were observed in 20 pregnancies (47%), including 35% with arterial hypertension (n = 15), 9% with pre-eclampsia (n = 4), 2% with HELLP syndrome (n = 1) and 14% with intrauterine growth restriction (IUGR, n = 6, leading in one case to a medically indicated termination of pregnancy). There were 42 live births (98%) at a median term of 38 [27-42] weeks gestation including 9 before 37 weeks (21%). The median birth weight was 2940 [610-4310] grams. Five children (12%) required transfer to a neonatal intensive care unit. One premature boy (27 weeks gestation) died after 2 days. Treatment during pregnancy included steroids (n = 25/43; 58%), azathioprine (n = 9/43; 21%) and infliximab (n = 1/43; 2%). The risk of developing arterial hypertension during pregnancy was associated with previous chronic arterial hypertension and with an infra-diaphragmatic vasculitis injury (P = 0.01 and P = 0.04, respectively). No correlation was reported between TAK activity and any of the obstetrical complications described in the study., Conclusion: This study showed a high rate of adverse obstetrical complications without significant impact on live birth rates. Pregnancy did not appear to influence TAK disease activity. Key Points • We observed a high rate of adverse obstetrical complications in women with Takayasu arteritis; however, the rate of live births was high. Pregnancy did not appear to influence TA disease activity.

The surgical outcome of brain tumor resection and needle biopsy is significantly correlated to the patient's prognosis. Brain tumor surgery is limited to resecting the solid portion of the tumor as current intraoperative imaging modalities are incapable of delineating infiltrative regions. For accurate delineation, in situ tissue interrogation at the submicron scale is warranted. Additionally, multimodal detection is required to remediate the genetically and molecularly heterogeneous nature of brain tumors, notably, that of gliomas, meningioma and brain metastasis. Multimodal detection, such as spectrally- and temporally-resolved fluorescence under one- and two-photon excitation, enables characterizing tissue based on several endogenous optical contrasts. In order to assign the optically-derived parameters to different tissue types, construction of an optical database obtained from biopsied tissue is warranted. This report showcases the different quantitative and semi-quantitative optical markers that may comprise the tissue discrimination database. These include: the optical index ratio, the optical redox ratio, the relative collagen density, spectrally-resolved fluorescence lifetime parameters, two-photon fluorescence imaging and second harmonic generation imaging., (© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Key Message: The comparison of QTL detection performed on an elite panel and an (elite [Formula: see text] exotic) progeny shows that introducing exotic germplasm into breeding programs can bring new interesting allelic diversity. Selection of stable varieties producing the highest amount of extractable sugar per hectare (ha), resistant to diseases, and respecting environmental criteria is undoubtedly the main target for sugar beet breeding. As sodium, potassium, and [Formula: see text]-amino nitrogen in sugar beets are the impurities that have the biggest negative impact on white sugar extraction, it is interesting to reduce their concentration in further varieties. However, domestication history and strong selection pressures have affected the genetic diversity needed to achieve this goal. In this study, quantitative trait locus (QTL) detection was performed on two populations, an (elite [Formula: see text] exotic) sugar beet progeny and an elite panel, to find potentially new interesting regions brought by the exotic accession. The three traits linked with impurities content were studied. Some QTLs were detected in both populations, the majority in the elite panel because of most statistical power. Some of the QTLs were colocated and had favorable effect in the progeny since the exotic allele was linked with a decrease in the impurity content. A few number of favorable QTLs were detected in the progeny, only. Consequently, introgressing exotic genetic material into sugar beet breeding programs can allow the incorporation of new interesting alleles.

Objective: To assess factors associated with favorable outcome in refractory insular epilepsy treated by volume-based stereotactic radiofrequency thermocoagulation (RFTC)., Methods: We performed volume-based RFTC in 19 patients (11 males, 7-44 years old). The volume for thermocoagulation was identified by multimodal data including electroencephalography (EEG)-video, magnetic resonance imaging (MRI), and fluorodeoxyglucose-positron emission tomography (PET) in all patients, and epileptogenic zone (EZ) was assessed by stereo-electroencephalography (SEEG) in 16. MRI showed insular lesions in four patients (benign tumors, n = 2; focal cortical dysplasia [FCD], n = 1; polymicrogyria, n = 1). MRI was negative in 15 cases; however, PET was positive in 18, and FCD pattern was detected by SEEG in nine cases. The dominant hemisphere was involved in 12 cases. RFTC was performed as a separate procedure after SEEG, or as a single MRI-guided procedure. The insular volume to be coagulated was determined by a tridimensional identification of the epileptogenic cortex using MRI, PET, and SEEG, and was destroyed with coalescent thermal lesions., Results: Seizure-free outcome was achieved in 10 patients (53%), including Engel class IA in three (follow-up = 1-12 years, mean = 5.4). The responder rate (including Engel classes I-III) was 89%. Transient postoperative deficits (mild hemiparesia, dysarthria, hypoesthesia, dysgeusia) were observed in eight patients (42%), with rapid and total recovery in all but one with persistent mild dysarthria. Neurological deficits were related to higher number of RFTC procedures (P = .036) and greater volume of RFTC (P = .028). Neuropsychological status was unchanged or improved in all; however, psychiatric status transitorily worsened in three patients. Factors contributing to seizure-free outcome were the detection of FCD pattern (P = .009), localized EZ (P = .038), low RFTC volume (P = .002), low number of RFTC procedures (P = .001), and low RFTC volume/number ratio (P = .012). Optimal volume of RFTC around 2 cm 3 offered the best compromise between efficacy and safety., Significance: RFTC may be curative in insular epilepsy after accurate localization of EZ with SEEG. Best outcome was associated with low volume of thermolesions., (Wiley Periodicals, Inc. © 2019 International League Against Epilepsy.)

Among all the tumors of the central nervous system (CNS), glioma are the most deadly and the most malignant. Surgical resection is the standard therapeutic method to treat this type of brain cancer. But the diffusive character of these tumors create many problems for surgeons during the operation. In fact, these tumors migrate outside the tumor solid zone and invade the surrounding healthy tissues. These infiltrative tissues have the same visual appearance as healthy tissues, making it very difficult for surgeons to distinguish the healthy ones from the diffused ones. The surgeon, therefore, cannot properly remove the tumor margins increasing the recurrence risk of the tumor. To resolve this problem, our team has developed a multimodal two-photon fibered endomicroscope, compatible with the surgeon trocar, to better delimitate tumor boundaries by relying on the endogenous fluorescence of brain tissues. In this context, and in order to characterize the optical signature of glioma tumors, this study offers multimodal and multi-scaled optical measurements from healthy tissues to high grade glioma. We can interrogate tissue from deep ultra-violet to near infrared excitation by working with spectroscopy, fluorescence lifetime imaging, two-photon fluorescene imaging and Second Harmonic Generation (SHG) imaging. Optically derived ratios such as the Tryptophan/Collagen ratio, the optical redox ratio and the long lifetime intensity fraction, discriminated diseased tissue from its normal counterparts when fitted by Gaussian ellipsoids and choosing a threshold for each. Additionally two-photon fluorescence and SHG images were shown to display similar histological features as Hematoxylin-Eosin stained images.

To complement a project toward label-free optical biopsy and enhanced resection which the overall goal is to develop a multimodal nonlinear endomicroscope, this multimodal approach aims to enhance the accuracy in classifying brain tissue into solid tumor, infiltration and normal tissue intraoperatively. Multiple optical measurements based on one- and two-photon spectral and lifetime autofluorescence, including second harmonic generation imaging, were acquired. As a prerequisite, studying the effect of the time of measurement postexcision on tissue's spectral/lifetime fluorescence properties was warranted, so spectral and lifetime fluorescences of fresh brain tissues were measured using a point-based linear endoscope. Additionally, a comparative study on tissue's optical properties obtained by multimodal nonlinear optical imaging microscope from fresh and fixed tissue was necessary to test whether clinical validation of the nonlinear endomicroscope is feasible by extracting optical signatures from fixed tissue rather than from freshly excised samples. The former is generally chosen for convenience. Results of this study suggest that an hour is necessary postexcision to have consistent fluorescence intensities\lifetimes. The fresh (a,b,c) vs fixed (d,e,f) tissue study indicates that while all optical signals differ after fixation. The characteristic features extracted from one- and two-photon excitation still discriminate normal brain (a,d) cortical tissue, glioblastoma (GBM) (b,e) and metastases (c,f)., (© 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

The primary line of therapy for high-grade brain tumor is surgical resection, however, identifying tumor margins in vivo remains a major challenge. Despite the progress in computer-assisted imaging techniques, biopsy analysis remains the standard diagnostic tool when it comes to delineating tumor margins. Our group aims to answer this challenge by exploiting optical imaging of endogenous fluorescence in order to provide a reliable and reproducible diagnosis close to neuropathology. In this study, we first establish the ability of two-photon microscopy (TPM) to discriminate normal brain tissue from glioblastomas and brain metastasis using the endogenous fluorescence response of fresh human brain sample. Two-photon fluorescence images were compared to gold standard neuropathology. "Blind" diagnosis realized by a neuropathologist on a group of TPM images show a good sensitivity, 100%, and specificity, 50% to discriminate non tumoral brain tissue versus glioblastoma or brain metastasis. Quantitative analysis on spectral and fluorescence lifetime measurements resulted in building a scoring system to discriminate brain tissue samples.

Accurate intraoperative tumour margin assessment is a major challenge in neurooncology, where sparse tumours beyond the bulk tumour are left undetected under conventional resection. Non-linear optical imaging can diagnose tissue at the sub-micron level and provide functional label-free histopathology in vivo. For this reason, a non-linear endomicroscope is being developed to characterize brain tissue intraoperatively based on multiple endogenous optical contrasts such as spectrally- and temporally-resolved fluorescence. To produce highly sensitive optical signatures that are specific to a given tissue type, short femtosecond pulsed lasers are required for efficient two-photon excitation. Yet, the potential of causing bio-damage has not been studied on neuronal tissue. Therefore, as a prerequisite to clinically testing the non-linear endomicroscope in vivo, the effect of short laser pulse durations (40-340 fs) on ex vivo brain tissue was investigated by monitoring the intensity, the spectral, and the lifetime properties of endogenous fluorophores under 800 and 890 nm two-photon excitation using a bi-modal non-linear endoscope. These properties were also validated by imaging samples on a benchtop multiphoton microscope. Our results show that under a constant mean laser power, excitation pulses as short as 40 fs do not negatively alter the biochemical/ biophysical properties of tissue even for prolonged irradiation.

The original version of this article has added numbers in the text which are unnecessary. Correct line should be: "We also performed PET/MRI based surgical resections in an increasing number of MRI negative/ doubtful cases with favourable outcome."

Purpose: To assess the localizing value of 18 F-FDG PET in patients operated on for drug-resistant epilepsy due to focal cortical dysplasia type 2 (FCD 2 )., Methods: We analysed 18 F-FDG PET scans from 103 consecutive patients (52 males, 7-65 years old) with histologically proven FCD 2 . PET and MRI data were first reviewed by visual analysis blinded to clinical information and FCD 2 location. The additional value of electroclinical data and PET/MRI coregistration was assessed by comparison with pathological results and surgical outcomes., Results: Visual analysis of PET scans showed focal or regional hypometabolism corresponding to the FCD 2 in 45 patients (44%), but the findings were doubtful or misleading in 37 patients and negative in 21. When considering electroclinical data, positive localization was obtained in 73 patients, and this increased to 85 (83%) after coregistration of PET and MRI data. Under the same conditions, MRI was positive in 61 patients (59%), doubtful in 15 and negative in 27. The additional value of PET was predominant in patients negative or doubtful on MRI, localizing the FCD 2 in 35 patients (83%). Interobserver agreement correlated with the grade of hypometabolism: it was good in patients with mild to severe hypometabolism (82-95%), but moderate in those with subtle/doubtful hypometabolism (45%). The main factors influencing positive PET localization were the grade of hypometabolism and the size of the FCD 2 (P < 0.0001). Misleading location (nine patients) was associated with a small FCD 2 in the mesial frontal and central regions. Following limited cortical resection mainly located in extratemporal areas (mean follow-up 5.6 years), a seizure-free outcome was achieved in 94% of patients, including Engel's class IA in 72%., Conclusion: In this series, 18 F-FDG PET contributed to the localization of FCD 2 in 83% of patients. This high localizing value was obtained by integration of electroclinical data and PET/MRI coregistration. This approach may help improve the surgical outcome in extratemporal epilepsy, even in patients negative on MRI.

Introduction: Malignant primary diffuse leptomeningeal gliomatosis (MPDLG) are rare central nervous system neoplasms associated with a poor outcome., Case Report: We report the case of a 40-year-old woman who presented with unusual worsening of bilateral sciatica, headaches, diplopia and a left proptosis. MRI of the head and spine showed multiple leptomeningeal lesions with no intra parenchymal involvement. The search for a primary tumor was negative. An open surgical biopsy of the prominent intradural lumbar tumor was performed within a week. Histopathology, immunochemistry and molecular analyses revealed a malignant glioma with histone H3.3 K27M mutation. The patient was referred to the neuro-oncologist for chemotherapy and craniospinal radiotherapy. Despite aggressive therapy, she died of disseminated tumoral progression, 18 weeks after the diagnosis., Conclusion: MPLG is a rare tumor which should be considered whenever a patient presents with diffuse or multinodular meningeal contrast-enhancing lesions. Some cases of MLPG share histological and immunophenotypical features with diffuse midline gliomas H3-K27M-mutant, a rapidly fatal disease. The diagnosis remains histopathological and, therefore a biopsy is obligatory without delay. Immunohistochemistry and/or molecular analyses are now currently essential for a formal classification and, to provide a better prediction of clinical outcome, particularly in this heterogeneous group of tumors., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Background: To report on the outcome of patients diagnosed with central nervous system haemangiopericytoma (HPC) or solitary fibrous tumours (SFT) and identify factors that may influence recurrence and survival., Material and Methods: Between January 1977 and December 2016, a retrospective search identified 22 HPCs/SFTs. The patients underwent a total of 40 surgical resections and 63.6% received radiotherapy. Median follow-up was 7.8 years., Results: Six patients (27.3%) were re-operated for tumour recurrence. At the end of the study, 15 patients (68.2%) had no residual tumour on the last imaging. Surgical recurrence-free survival at 5 years was 77.4%, [95% CI: 60.1-99.8]. None of the investigated variables was associated with recurrence. At the end of the study, 5 patients were deceased (22.7%) and only 10 patients (45.5%) had no residual tumour on the last imaging and were alive. Overall survival at 5 years was 95%, [95% CI: 85.9-100]. None of the investigated variables was associated with overall survival. Patients who received radiotherapy demonstrated neither a reduced risk of surgical recurrence (P=0.378) nor a longer overall survival (P=0.405)., Conclusion: SFTs/HPCs are associated with a significant risk of recurrence that may reduce the survival. Even if we could not demonstrate their benefit in this limited series, we believe that tailored maximal tumour resection on initial surgery is beneficial and that adjuvant RT is useful for tumours displaying grade II or III, even in case of complete removal., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

We propose expert recommendations on the use of SEEG-guided radiofrequency thermocoagulation (RF-TC) based on an exhaustive literature review. This technique consists in performing a RF-TC lesion using a SEEG depth electrode at the end of the recording. It is indicated when conventional surgical resection of the ictal onset zone is not possible. SEEG guided RF-TC can also be considered as a diagnostic tool since an improvement, even limited, has a high positive predictive value concerning the good outcome after surgery. It is possible to perform SEEG only in the purposes of performing RF-TC. An over-implantation of the presumed ictal onset zone is possible when such a procedure is planned. The RF-TC target should only be defined based on the ictal activity, except when a type II focal cortical dysplasia electrophysiological interictal signature is recorded. A single or multiple coagulations should always be performed between contiguous electrode contacts. The power delivered by the generator should be increased until the impedance suddenly changes, which indicates that the thermocoagulation has occurred. The procedure should be performed under clinical monitoring without anesthesia and after systematically testing neurological functions by electric stimulation on each target. Multiple SEEG-guided RF-TC can be proposed in a single patient, for example, in cases of relapse after a previous effective procedure. Conventional resection surgery remains feasible after a RF-TC procedure., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

Stereoelectroencephalography (SEEG) was designed and developed in the 1960s in France by J. Talairach and J. Bancaud. It is an invasive method of exploration for drug-resistant focal epilepsies, offering the advantage of a tridimensional and temporally precise study of the epileptic discharge. It allows anatomo-electrical correlations and tailored surgeries. Whereas this method has been used for decades by experts in a limited number of European centers, the last ten years have seen increasing worldwide spread of its use. Moreover in current practice, SEEG is not only a diagnostic tool but also offers a therapeutic option, i.e., thermocoagulation. In order to propose formal guidelines for best clinical practice in SEEG, a working party was formed, composed of experts from every French centre with a large SEEG experience (those performing more than 10 SEEG per year over at least a 5 year period). This group formulated recommendations, which were graded by all participants according to established methodology. The first part of this article summarizes these within the following topics: indications and limits of SEEG; planning and management of SEEG; surgical technique; electrophysiological technical procedures; interpretation of SEEG recordings; and SEEG-guided radio frequency thermocoagulation. In the second part, those different aspects are discussed in more detail by subgroups of experts, based on existing literature and their own experience. The aim of this work is to present a consensual French approach to SEEG, which could be used as a basic document for centers using this method, particularly those who are beginning SEEG practice. These guidelines are supported by the French Clinical Neurophysiology Society and the French chapter of the International League Against Epilepsy., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

In SEEG, as for any surgical procedure, the benefit/risk ratio is a key-point. This implies rigorous clinical practice in terms of indication, information delivered to the patient, and surgical technique. Numerous technical options may be used to achieve this goal. All are valuable, as long as they are executed with rigor and consistency. Intracranial bleeding represents the main risk of the procedure (1-4% of cases). The procedure also carries a risk of infection (0.8%), death (total of 6 reported cases in all the literature, <0.002%), and of minor and transient side effects. SEEG is performed under general anesthesia. MRI is the gold standard morphological imaging, used for targeting and for trajectory calculations. It is strictly necessary to use some form of vascular imaging to minimize the peroperative bleeding risk. SEEG can be performed on a frame-based, or frameless, basis, using stereotactic instrumentation, or a neurosurgical robot. Literature does not provide any data in favour of one of these techniques compared to the other. The minimal acceptable bone thickness is considered to be 2mm. Postoperatively, as soon as any non-preexisting neurological deficit is noticed, neuroimaging must immediately be performed. It is recommended to perform a postoperative imaging during the 24hours after implantation. The numerous current possibilities, in terms of imaging and technology, give rise to many possible stereotactic strategies for performing SEEG implantation. None of these strategies can be considered as superior to the other. The guarantee of the best possible result is provided by the care with which these procedures are done., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

The authors report on a patient harbouring an unruptured cortical arteriovenous malformation (AVM), who had presented with obstructive hydrocephalus due to compression of the cerebral aqueduct by a large venous varix. A ventriculoperitoneal (VP) shunt was inserted in emergency. Due to its large volume, the AVM was not referred for treatment and a follow-up policy was chosen. After the second VP shunt dysfunction, endoscopic third ventriculostomy was performed under neuronavigation. The procedure went uneventfully and the patient recovered well. In the rare eventuality of obstructive hydrocephalous caused by an unruptured AVM, endoscopic third ventriculostomy is feasible, efficient and can avoid shunt-related complications.

Epilepsy surgery. Epilepsy surgery is indicated for adults or children with partial, drug-resistant and disabling epilepsy. It has developed over the last few decades through better identification of candidates, advances in imaging and surgical techniques. Main indications are temporal lobe epilepsy associated with hippocampal sclerosis, low-grade glial tumors and focal cortical dysplasia. Pre-surgical assessment is based on clinical, neurophysiological and imaging data which most often allow to carry the surgical indication. A neuropsychological and psychiatric assessment is essential to investigate the comorbidities and evaluate the risk of post-operative decompensation. Intracerebral exploration using stereotactic implanted electrodes (stereo-electroencephalography) may be necessary to identify the epileptogenic zone and define the surgical strategy. Resection surgery (corticectomy or lesionectomy) is the most common procedure. Seizure-free outcome is obtained in 60-80% of patients after surgery, with a low morbidity. These results are maintained over the long term and associated by an improvement in the quality of life and a reduction in the costs of the disease. Best results are observed in young subjects with short epilepsy duration., Competing Interests: F. Chassoux déclare des liens ponctuels (interventions ponctuelles, prise en charge lors de congrès) avec UCB. B. Devaux déclare ne pas avoir de liens d’intérêts.

A key challenge of central nervous system tumor surgery is to discriminate between brain regions infiltrated by tumor cells and surrounding healthy tissue. Although monitoring of autofluorescence could potentially be an efficient way to provide reliable information for these regions, we found little information on this subject, and thus we conducted studies of brain tissue optical properties. This particular study focuses on the different optical quantitative responses of human central nervous system tumors and their corresponding controls. Measurements were performed on different fixed human tumoral and healthy brain samples. Four groups of central nervous system tumors (glioblastoma, diffuse glioma, meningioma and metastasis) were discriminated from healthy brain and meninx control tissues. A threshold value was found for the scattering and absorption coefficient between tumoral and healthy groups. Emission Spectra of healthy tissue had a significant higher intensity than tumoral groups. The redox and optical index ratio were thenn calculated and these also showed significant discrimination. Two fluorescent molecules, NADH and porphyrins, showed distinct lifetim values among the different groups of samples. This study defines several optical indexes that can act as combinated indicators to discriminate healthy from tumoral tissues.

For newly diagnosed glioblastomas treated with resection in association with the standard combined chemoradiotherapy, the impact of Carmustine wafer implantation remains debated regarding postoperative infections, quality of life, and feasibility of adjuvant oncological treatments. To assess together safety, tolerance and efficacy of Carmustine wafer implantation and of extent of resection for glioblastoma patients in real-life experience. Observational retrospective monocentric study including 340 consecutive adult patients with a newly diagnosed supratentorial glioblastoma who underwent surgical resection with (n = 123) or without (n = 217) Carmustine wafer implantation as first-line oncological treatment. Carmustine wafer implantation and extent of resection did not significantly increase postoperative complications, including postoperative infections (p = 0.269, and p = 0.446, respectively). Carmustine wafer implantation and extent of resection did not significantly increase adverse events during adjuvant oncological therapies (p = 0.968, and p = 0.571, respectively). Carmustine wafer implantation did not significantly alter the early postoperative Karnofsky performance status (p = 0.402) or the Karnofsky performance status after oncological treatment (p = 0.636) but a subtotal or total surgical resection significantly improved those scores (p < 0.001, and p < 0.001, respectively). Carmustine wafer implantation, subtotal and total resection, and standard combined chemoradiotherapy were independently associated with longer event-free survival (adjusted Hazard Ratio (aHR), 0.74 [95% CI 0.55-0.99], p = 0.043; aHR, 0.70 [95% CI 0.54-0.91], p = 0.009; aHR, 0.40 [95% CI 0.29-0.55], p < 0.001, respectively) and with longer overall survival (aHR, 0.69 [95% CI 0.49-0.96], p = 0.029; aHR, 0.52 [95% CI 0.38-0.70], p < 0.001; aHR, 0.58 [95% CI 0.42-0.81], p = 0.002, respectively). Carmustine wafer implantation in combination with maximal resection, followed by standard combined chemoradiotherapy is safe, efficient, and well-tolerated in newly diagnosed supratentorial glioblastomas in adults.

Sainte-Anne Hospital is the largest psychiatric hospital in Paris. Its long and fascinating history began in the 18th century. In 1952, it was at Sainte-Anne Hospital that Jean Delay and Pierre Deniker used the first neuroleptic, chlorpromazine, to cure psychiatric patients, putting an end to the expansion of psychosurgery. The Department of Neuro-psychosurgery was created in 1941. The works of successive heads of the Neurosurgery Department at Sainte-Anne Hospital summarized the history of psychosurgery in France. Pierre Puech defined psychosurgery as the necessary cooperation between neurosurgeons and psychiatrists to treat the conditions causing psychiatric symptoms, from brain tumors to mental health disorders. He reported the results of his series of 369 cases and underlined the necessity for proper follow-up and postoperative re-education, illustrating the relative caution of French neurosurgeons concerning psychosurgery. Marcel David and his assistants tried to follow their patients closely postoperatively; this resulted in numerous publications with significant follow-up and conclusions. As early as 1955, David reported intellectual degradation 2 years after prefrontal leucotomies. Jean Talairach, a psychiatrist who eventually trained as a neurosurgeon, was the first to describe anterior capsulotomy in 1949. He operated in several hospitals outside of Paris, including the Sarthe Psychiatric Hospital and the Public Institution of Mental Health in the Lille region. He developed stereotactic surgery, notably stereo-electroencephalography, for epilepsy surgery but also to treat psychiatric patients using stereotactic lesioning with radiofrequency ablation or radioactive seeds of yttrium-90. The evolution of functional neurosurgery has been marked by the development of deep brain stimulation, in particular for obsessive-compulsive disorder, replacing the former lesional stereotactic procedures. The history of Sainte-Anne Hospital's Neurosurgery Department sheds light on the initiation-yet fast reconsideration-of psychosurgery in France. This relatively more prudent attitude toward the practice of psychosurgery compared with other countries was probably due to the historically strong collaboration between psychiatrists and neurosurgeons in France.

Introduction: Dysembryoplastic neuroepithelial tumors and gangliogliomas are developmental glioneuronal tumors usually revealed by partial epilepsy. High epileptogenicity, childhood epilepsy onset, drug-resistance, temporal location, and seizure freedom after complete resection are common characteristics of both tumors. We report the specificity of surgical management, functional results and seizure outcome in cases of a tumor location in eloquent areas., Methods: Among 150 patients (88 males, 3-55 years) operated on for refractory epilepsy due to a glioneuronal tumor (1990-2015), 30 (20%, dysembryoplastic neuroepithelial tumors=21; gangliogliomas=9) had a tumor located in an eloquent cortex (sensory-motor, insular or language areas). Surgery was performed after a preoperative work-up, including stereo-electroencephalography in 48 patients (26%) and functional MRI in 100 (67%). MRI-guided lesionectomy was mainly performed in extra-temporal location, whereas an additional corticectomy was performed in a temporal location. Tumor microsurgical resections were guided using neuronavigation and cortical/subcortical electrical stimulations. Multiple stereotactic thermocoagulations were performed in two insular tumors., Results: New motor/language deficits related to eloquent areas occurred postoperatively in 6/30 patients (20%) without any major permanent disability. Minor sensorimotor (n=2) and moderate language disturbance (n=1) persisted in three of them. Postoperative seizure-free outcome (mean follow-up>5 years) was obtained in 81% of the entire series, but significantly decreased to 60% in eloquent areas. Incomplete tumor resection was the main cause of surgical failure. However, unfavorable seizure outcome was also observed despite complete tumor resection. Malignant transformation occurred in one ganglioglioma., Conclusion: Epilepsy surgery for benign glioneuronal tumors in eloquent areas provides acceptable results regarding the functional risks. Complete tumor resection is crucial for long-term favorable outcome., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

Aim: Prevalence and predictors of epileptic seizures are unknown in the malignant variant of ganglioglioma., Methods: In a retrospective exploratory dataset of 18 supratentorial anaplastic World Health Organization grade III gangliogliomas, we studied: (i) the prevalence and predictors of epileptic seizures at diagnosis; (ii) the evolution of seizures during tumor evolution; (iii) seizure control rates and predictors of epilepsy control after oncological treatments., Results: Epileptic seizures prevalence progresses throughout the natural course of anaplastic gangliogliomas: 44% at imaging discovery, 67% at histopathological diagnosis, 69% following oncological treatment, 86% at tumor progression, and 100% at the end-of-life phase. The medical control of seizures and their refractory status worsened during the tumor's natural course: 25% of uncontrolled seizures at histopathological diagnosis, 40% following oncological treatment, 45.5% at tumor progression, and 45.5% at the end-of-life phase. Predictors of seizures at diagnosis appeared related to the tumor location (i.e. temporal and/or cortical involvement). Prognostic parameters of seizure control after first-line oncological treatment were temporal tumor location, eosinophilic granular bodies, TP53 mutation, and extent of resection. Prognostic parameters of seizure control at tumor progression were a history of epileptic seizures at diagnosis, seizure control after first-line oncological treatment, eosinophilic granular bodies, and TP53 mutation., Conclusion: Epileptic seizures are frequently observed in anaplastic gangliogliomas and both prevalence and medically refractory status worsen during the tumor's natural course. Both oncological and antiepileptic treatments should be employed to improve the control of epileptic seizures and the quality of life of patients harboring an anaplastic ganglioglioma.

Introduction: The value of ultrasound guidance for intermediate cervical blocks in patients undergoing carotid artery endarterectomy is poorly described. This study aimed at comparing the efficacy of ultrasound-guided intermediate cervical block to superficial cervical block for carotid artery endarterectomies., Patients and Methods: We conducted a single-centre randomized-controlled study in a French University Hospital, from April 2011 to March 2012. The anaesthesia technique was randomly allocated to patients scheduled for carotid artery endarterectomy under regional anaesthesia (ropivacaine 4.75mg/mL): superficial cervical block in the Control group, and ultrasound-guided intermediate cervical block in the Echo group. The main outcome measure was the percentage of surgery performed without supplemental topical anaesthesia. The secondary outcomes were: rate of conversion to general anaesthesia, amount of supplemental topical lidocaine and block-related complications. P<0.05 was considered significant., Results: Demographic data for the 86 patients included [mean (SD) age 73 (11) years] did not differ between groups. Surgery was performed without supplemental topical lidocaine in 23% and 7% of the patients in the Echo and Control groups, respectively (P=0.068). Conversion to general anaesthesia for inadequate analgesia was needed in 0 and 2 patients in the Echo and Control groups, respectively. The mean dose of topical lidocaine was not different between groups. No complication directly related to a cervical block was observed., Conclusions: Ultrasound-guided intermediate cervical plexus block and superficial cervical blocks performed for carotid artery surgery seems to provide similar results, but this study was probably underpowered to detect any difference., Trial Registration: European Union Drug Regulating Authorities Clinical Trials (Eudra-CT) registration number: 2010-A 01490-39., (Copyright © 2016 Société française d'anesthésie et de réanimation (Sfar). Published by Elsevier Masson SAS. All rights reserved.)

Cell populations with differing proliferative, stem-like and tumorigenic states co-exist in most tumors and especially malignant gliomas. Whether metabolic variations can drive this heterogeneity by controlling dynamic changes in cell states is unknown. Metabolite profiling of human adult glioblastoma stem-like cells upon loss of their tumorigenicity revealed a switch in the catabolism of the GABA neurotransmitter toward enhanced production and secretion of its by-product GHB (4-hydroxybutyrate). This switch was driven by succinic semialdehyde dehydrogenase (SSADH) downregulation. Enhancing GHB levels via SSADH downregulation or GHB supplementation triggered cell conversion into a less aggressive phenotypic state. GHB affected adult glioblastoma cells with varying molecular profiles, along with cells from pediatric pontine gliomas. In all cell types, GHB acted by inhibiting α-ketoglutarate-dependent Ten-eleven Translocations (TET) activity, resulting in decreased levels of the 5-hydroxymethylcytosine epigenetic mark. In patients, low SSADH expression was correlated with high GHB/α-ketoglutarate ratios, and distinguished weakly proliferative/differentiated glioblastoma territories from proliferative/non-differentiated territories. Our findings support an active participation of metabolic variations in the genesis of tumor heterogeneity.

Objective: To search for [ 18 F]-fluorodeoxyglucose (FDG)-PET patterns predictive of long-term prognosis in surgery for drug-resistant mesial temporal lobe epilepsy (MTLE) due to hippocampal sclerosis (HS)., Methods: We analyzed metabolic data with [ 18 F]-FDG-PET in 97 patients with MTLE (53 female participants; age range 15-56 years) with unilateral HS (50 left) and compared the metabolic patterns, electroclinical features, and structural atrophy on MRI in patients with the best outcome after anteromesial temporal resection (Engel class IA, completely seizure-free) to those with a non-IA outcome, including suboptimal outcome and failure. Imaging processing was performed with statistical parametric mapping (SPM5)., Results: With a mean follow-up of >6 years (range 2-14 years), 85% of patients achieved a class I outcome, including 45% in class IA. Class IA outcome was associated with a focal anteromesial temporal hypometabolism, whereas non-IA outcome correlated with extratemporal metabolic changes that differed according to the lateralization: ipsilateral mesial frontal and perisylvian hypometabolism in right HS and contralateral fronto-insular hypometabolism and posterior white matter hypermetabolism in left HS. Suboptimal outcome presented a metabolic pattern similar to the best outcome but with a larger involvement of extratemporal areas, including the contralateral side in left HS. Failure was characterized by a mild temporal involvement sparing the hippocampus and relatively high extratemporal hypometabolism on both sides. These findings were concordant with electroclinical features reflecting the organization of the epileptogenic zone but were independent of the structural abnormalities detected on MRI., Conclusions: [ 18 F]-FDG-PET patterns help refine the prognostic factors in MTLE and should be implemented in predictive models for epilepsy surgery., (© 2017 American Academy of Neurology.)

Objective: To analyze the outcome of epileptic patients who had redo surgery involving the vagus nerve stimulation's lead., Methods: We reviewed the clinical and surgical records of all patients who had a complete vagus nerve stimulation (VNS) removal or replacement or any redo surgical procedure involving the system lead at Sainte-Anne Hospital in Paris, France., Results: Between the years 1999 and 2016, 41 redo surgical procedures involving the lead or electrode were achieved, of which 23 were complete VNS explantations, 12 were complete system replacements, 5 were lead changes only, and 1 was isolated lead removal. 41% of the surgical procedures were achieved in female patients. This population has a median age at VNS implantation of 33.6 years (interquartile range [IQR], [21.4-38.6]. Median time between the VNS implantation and the redo surgery involving the lead was 4.9 years (IQR, 2.9-8). The reason for VNS removal was mainly a lack of clinical effectiveness. No preoperative or postoperative complications occurred after complete VNS system removal or lead replacement. The effectiveness of the VNS therapy remained unchanged after lead replacement. No vagus nerve injury was reported, nor did symptoms suggest that it was disabled., Conclusions: Complete removal or replacement of the VNS system including the lead and the electrode is feasible and safe. These procedures should be offered to patients who would no longer benefit from the VNS or when only a lead change is needed., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Delineating tumor margins as accurately as possible is of primordial importance in surgical oncology: extent of resection is associated with survival but respect of healthy surrounding tissue is necessary for preserved quality of life. The real-time analysis of the endogeneous fluorescence signal of brain tissues is a promising tool for defining margins of brain tumors. The present study aims to demonstrate the feasibility of multimodal optical analysis to discriminate fresh samples of gliomas, metastases and meningiomas from their appropriate controls. Tumor samples were studied on an optical fibered endoscope using spectral and fluorescence lifetime analysis and then on a multimodal set-up for acquiring spectral, one and two-photon fluorescence images, second harmonic generation signals and two-photon fluorescence lifetime datasets. The obtained data allowed us to differentiate healthy samples from tumor samples. These results confirmed the possible clinical relevance of this real-time multimodal optical analysis. This technique can be easily applied to neurosurgical procedures for a better delineation of surgical margins., Competing Interests: The authors declare no competing financial interests.

Meningioma is the most frequent primary central nervous system tumor. The risk of recurrence and the prognosis are correlated with the extent of the resection that ideally encompasses the infiltrated dura mater and, if required, the infiltrated bone. No device can deliver real-time intraoperative histopathological information on the tumor environment to help the neurosurgeon to achieve a gross total removal. This study assessed the abilities of nonlinear microscopy to provide relevant and real-time data to help resection of meningiomas. Nine human meningioma samples (four World Health Organization Grade I, five Grade II) were analyzed using different optical modalities: spectral analysis and imaging, lifetime measurements, fluorescence lifetime imaging microscopy, fluorescence emitted under one- and two-photon excitation and the second-harmonic generation signal imaging using a multimodal setup. Nonlinear microscopy produced images close to histopathology as a gold standard. The second-harmonic generation signal delineated the collagen background and two-photon fluorescence underlined cell cytoplasm. The matching between fluorescence images and Hematoxylin and Eosin staining was possible in all cases. Grade I meningioma emitted less autofluorescence than Grade II meningioma and Grade II meningioma exhibited a distinct lifetime value. Autofluorescence was correlated with the proliferation rates and seemed to explain the observed differences between Grade I and II meningiomas. This preliminary multimodal study focused on human meningioma samples confirms the potential of tissue autofluorescence analysis and nonlinear microscopy in helping intraoperatively neurosurgeons to reach the actual boundaries of the tumor infiltration. Correspondence between H&E staining (top pictures) and the two-photon fluorescence imaging (bottom pictures)., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

OBJECTIVE There are no guidelines for the management of postoperative lateral sinus thrombosis following posterior fossa surgery. Introducing treatment-dose anticoagulant therapy during the immediate postoperative period increases the risk of intracranial bleeding. This study assessed the incidence of and risk factors associated with postoperative lateral sinus thrombosis and the complications related to thrombosis and/or anticoagulation. METHODS This study was a retrospective monocentric analysis of adult patients who underwent surgical removal of a posterior fossa space-occupying lesion with available postoperative imaging. Postoperative lateral sinus thrombosis was defined as a T2 * hypointensity within the venous sinus and/or a filling defect on postcontrast MRI or CT scan. RESULTS Among 180 patients, 12 (6.7%; 95% CI 3.0-10.4) were found to have lateral sinus thrombosis on postoperative imaging, none of whom were symptomatic. Unadjusted risk factors for postoperative lateral sinus thrombosis were a history of deep venous thrombosis (p = 0.016), oral contraceptive pill (p = 0.004), midline surgical approach (p = 0.035), and surgical exposure of the sinus (p < 0.001). Seven of the patients (58.3%) with a postoperative lateral sinus thrombosis received immediate treatment-dose anticoagulant therapy. Lateral sinus recanalization occurred radiologically at a mean time of 272 ± 23 days in 85.7% of patients (6 of 7) undergoing treatment-dose anticoagulant therapy and in 20% of patients (1 of 5) not receiving treatment-dose anticoagulant therapy. Postoperative complications occurred in 56.2% of patients (9 of 16) who received treatment-dose curative anticoagulant therapy and in 27% of patients (45 of 164) who did not. CONCLUSIONS Incidental radiological lateral sinus thrombosis following posterior fossa surgery has an incidence of 6.7%. To further define the benefit-to-risk ratio of a treatment-dose anticoagulant therapy, a prospective trial should be considered.

We present a customized small-core double-clad photonic crystal fiber for spectral and fluorescence lifetime measurements of human samples. In this Letter, the new fiber has been characterized on different fluorophores and samples of human brain tumor; a comparison to a bi-fiber homemade system and a commercial fiber probe was made.

Anaplastic ganglioglioma (AGG) is a rare and malignant variant of ganglioglioma. According to the World Health Organization classification version 2016, their histopathological grading criteria are still ill-defined. The aim of the present study was to assess the clinical, imaging, histopathological, and molecular characteristics and outcomes of AGGs in a large consecutive and retrospective adult and pediatric case series. Eighteen patients with AGGs (13 adults and 5 children) were identified (14 de novo and 4 secondary) from a cohort of 222 gangliogliomas (GG) (8%) treated at our institution between 2000 and 2015. AGGs represented a very aggressive disease with poor outcome (median progression-free survival, 10 months; median overall survival, 27 months). They were located in the temporal lobe only in 22% and presented with seizures (44%) or increased intracranial pressure (44%) at diagnosis. Concerning histopathological and molecular data, they shared morphological characteristics and BRAF V600E mutation (39%) with their benign counterparts but also showed hTERT promoter mutation (61%), p53 accumulation (39%), ATRX loss (17%), or p.K27M H3F3A mutation (17%). AGGs are malignant neoplasms requiring aggressive oncological treatment. In the perspective of targeted therapies, AGGs should be screened for BRAF V600E, hTERT, ATRX, and mutations of histone genes., (© 2016 American Association of Neuropathologists, Inc. All rights reserved.)

Objectives: To prospectively evaluate the predictive value of cerebral perfusion-computerized tomography (CTP) parameters variation between day0 and day4 after aneurysmal subarachnoid haemorrhage (aSAH)., Methods: Mean transit time (MTT) and cerebral blood flow (CBF) values were compared between patients with delayed cerebral ischemia (DCI+ group) and patients without DCI (DCI- group) for previously published optimal cutoff values and for variations of MTT (ΔMTT) and of CBF (ΔCBF) values between day0 and day4. DCI+ was defined as a cerebral infarction on 3-months follow-up MRI., Results: Among 47 included patients, 10 suffered DCI+. Published optimal cutoff values did not predict DCI, either at day0 or at day4. Conversely, ΔMTT and ΔCBF significantly differed between the DCI+ and DCI- groups, with optimal ΔMTT and ΔCBF values of 0.91 seconds (83.9 % sensitivity, 79.5 % specificity, AUC 0.84) and -7.6 mL/100 g/min (100 % sensitivity, 71.4 % specificity, AUC 0.86), respectively. In multivariate analysis, ΔCBF (OR = 1.91, IC95% 1.13-3.23 per each 20 % decrease of ΔCBF) and ΔMTT values (OR = 14.70, IC95% 4.85-44.52 per each 20 % increase of ΔMTT) were independent predictors of DCI., Conclusions: Assessment of MTT and CBF value variations between day0 and day4 may serve as an early imaging surrogate for prediction of DCI in aSAH., Key Points: • CT perfusion values are an imaging surrogate for prediction of DCI. • Early variations (day0-day4) after aneurysmal subarachnoid haemorrhage predicted DCI. • A CBF decrease of 7.6 mL/min/100 g predicted DCI with 100 % sensitivity. • An MTT increase of 0.91 seconds predicted DCI with 83.9 % sensitivity. • DCI risk multiplied by 2 per 20 % ΔCBF decrease and by 15 per 20 % ΔMTT increase.

Objective: To determine the main factors influencing metabolic changes in mesial temporal lobe epilepsy (MTLE) due to hippocampal sclerosis (HS)., Methods: We prospectively studied 114 patients with MTLE (62 female; 60 left HS; 15- to 56-year-olds) with (18) F-fluorodeoxyglucose-positron emission tomography and correlated the results with the side of HS, structural atrophy, electroclinical features, gender, age at onset, epilepsy duration, and seizure frequency. Imaging processing was performed using statistical parametric mapping., Results: Ipsilateral hypometabolism involved temporal (mesial structures, pole, and lateral cortex) and extratemporal areas including the insula, frontal lobe, perisylvian regions, and thalamus, more extensively in right HS (RHS). A relative increase of metabolism (hypermetabolism) was found in the nonepileptic temporal lobe and in posterior areas bilaterally. Voxel-based morphometry detected unilateral hippocampus atrophy and gray matter concentration decrease in both frontal lobes, more extensively in left HS (LHS). Regardless of the structural alterations, the topography of hypometabolism correlated strongly with the extent of epileptic networks (mesial, anterior-mesiolateral, widespread mesiolateral, and bitemporal according to the ictal spread), which were larger in RHS. Notably, widespread perisylvian and bitemporal hypometabolism was found only in RHS. Mirror hypermetabolism was grossly proportional to the hypometabolic areas, coinciding partly with the default mode network. Gender-related effect was significant mainly in the contralateral frontal lobe, in which metabolism was higher in female patients. Epilepsy duration correlated with the contralateral temporal metabolism, positively in LHS and negatively in RHS. Opposite results were found with age at onset. High seizure frequency correlated negatively with the contralateral metabolism in LHS., Significance: Epileptic networks, as assessed by electroclinical correlations, appear to be the main determinant of hypometabolism in MTLE. Compensatory mechanisms reflected by a relative hypermetabolism in the nonepileptic temporal lobe and in extratemporal areas seem more efficient in LHS and in female patients, whereas long duration, late onset of epilepsy, and high seizure frequency may reduce these adaptive changes., (Wiley Periodicals, Inc. © 2016 International League Against Epilepsy.)

A variety of drugs targeting monoamine receptors are routinely used in human pharmacology. We assessed the effect of these drugs on the viability of tumor-initiating cells isolated from patients with glioblastoma. Among the drugs targeting monoamine receptors, we identified prazosin, an α1- and α2B-adrenergic receptor antagonist, as the most potent inducer of patient-derived glioblastoma-initiating cell death. Prazosin triggered apoptosis of glioblastoma-initiating cells and of their differentiated progeny, inhibited glioblastoma growth in orthotopic xenografts of patient-derived glioblastoma-initiating cells, and increased survival of glioblastoma-bearing mice. We found that prazosin acted in glioblastoma-initiating cells independently from adrenergic receptors. Its off-target activity occurred via a PKCδ-dependent inhibition of the AKT pathway, which resulted in caspase-3 activation. Blockade of PKCδ activation prevented all molecular changes observed in prazosin-treated glioblastoma-initiating cells, as well as prazosin-induced apoptosis. Based on these data, we conclude that prazosin, an FDA-approved drug for the control of hypertension, inhibits glioblastoma growth through a PKCδ-dependent mechanism. These findings open up promising prospects for the use of prazosin as an adjuvant therapy for glioblastoma patients., (© 2016 The Authors. Published under the terms of the CC BY 4.0 license.)

Gap junctions (GJ) have been implicated in the synchronization of epileptiform activities induced by 4-aminopyrine (4AP) in slices from human epileptogenic cortex. Previous evidence implicated glial GJ to govern the frequency of these epileptiform events. The synchrony of these events (evaluated by the phase unlocking index, PUI) in adjacent areas however was attributed to neuronal GJ. In the present study, we have investigated the effects of GAP-134, a recently developed specific activator of glial GJ, on both the PUI and the frequency of the 4AP-induced epileptiform activities in human neocortical slices of temporal lobe epilepsy tissue. To delineate the impact of GJ on spatial spread of synchronous activity we evaluated the effects of carbenoxolone (CBX, a non-selective GJ blocker) on the spread in three axes 1. vertically in a given cortical column, 2. laterally within the deep cortical layers and 3. laterally within the upper cortical layers. GAP-134 slightly increased the frequency of the 4AP-induced spontaneous epileptiform activities while leaving the PUI unaffected. CBX had no effect on the PUI within a cortical column or on the PUI in the deep cortical layers. CBX increased the PUI for long interelectrodes distances in the upper cortical layers. In conclusion we provide new arguments toward the role played by glial GJ to maintain the frequency of spontaneous activities. We show that neuronal GJ control the PUI only in upper cortical layers., (Copyright © 2016 Elsevier B.V. All rights reserved.)