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International audience; Background: Herpes simplex encephalitis (HSE) and glioblastoma multiforme (GBM) co-occurrence has been described in few cases presenting immunocompromised status related to chemotherapy or chemoradiotherapy. Focal encephalitis over surgical edge of resection occurring shortly after GBM resection is rarely reported, and such infection has never been reported in low-grade glioma with secondary malignant transformation (i.e., secondary GBM). Here, we report a case of HSE misdiagnosed in the early postoperative course following a secondary GBM resection. We also provide a review of the literature about HSE occurring after glioma surgery. Case description: We report a case of an acute HSE with a fatal outcome occurring shortly after surgery for a secondary GBM. The patient presented with hyperthermia 12 days after the surgery and was treated with empirical antibiotics. She later suffered from seizure and neurologic deterioration, leading to death despite delayed antiviral administration. Magnetic resonance imaging revealed considerable fluid-attenuated inversion-recovery signal progression at the edge of the surgical resection and polymerase chain reaction amplification of herpes simplex virus (HSV) 1 DNA was positive. Conclusions: Clinicians should be aware of the existing co-occurrence between HSV infections and GBM during the postoperative course. Cerebrospinal fluid analysis with HSV polymerase chain reaction testing should be promptly undertaken, and some keys clinical elements should justify early empirical treatment, including acyclovir administration. The significant prognostic implication of HSE complicating GBM must raise the attention of neurosurgeon and neuro-oncologist about this entity.

International audience; Hypothèse.-Les fixations percutanées par vis pédiculaire (FPVP) (FPVP) sont de plus en plus pratiquées en chirurgie du rachis, minimisant la morbidité via un moindre délabrement musculaire mais au prix d'un guidage fluoroscopique peropératoire générant une forte exposition aux rayonnements. Peu d'études ont été conduites pour les mesurer précisément. L'objectif de notre étude est de quantifier, lors d'une PPSF réa-lisé dans différents centres expérimentés respectant les recommandations actuelles de radioprotection, cette irradiation reç ue au niveau du chirurgien et du patient. Matériel et méthodes.-Nous avons inclus prospectivement 100 procédures de FPVP pour lesquelles nous avons relevé les doses d'irradiation de l'opérateur principal. Pour chaque intervention, les doses du rayonnement absorbées sur le corps entier, les cristallins et les extrémités ont été mesurées. Résultats.-Nos résultats montrent une dose d'exposition moyenne par procédure sur le corps entier, les extrémités et les cristallins qui atteint respectivement, 1,7 ± 2,8 Sv, 204,7 ± 260,9 Sv et 30,5 ± 25,9 Sv. Discussion.-Selon ses valeurs, l'exposition des extrémités et des cristallins du chirurgien dépassera la limite annuelle admise par la Commission internationale de protection radiologique (CIPR) après respectivement 2440 et 4840 procédures. Conclusion.-Les directives récentes européennes vont réduire la dose d'exposition oculaire annuelle maximale de 150 à 20 mSv. Le nombre d'interventions chirurgicales pour ne pas atteindre le seuil oculaire, selon nos résultats, ne devra pas dépasser 645 procédures par an. Dans l'attente de la démocratisation des systèmes de neuronavigations, l'utilisation de la fluoroscopie conventionnelle expose les yeux en premier lieu et doivent donc être protégé par des verres plombés.

Hypothese Les fixations percutanees par vis pediculaire (FPVP) (FPVP) sont de plus en plus pratiquees en chirurgie du rachis, minimisant la morbidite via un moindre delabrement musculaire mais au prix d’un guidage fluoroscopique peroperatoire generant une forte exposition aux rayonnements. Peu d’etudes ont ete conduites pour les mesurer precisement. L’objectif de notre etude est de quantifier, lors d’une PPSF realise dans differents centres experimentes respectant les recommandations actuelles de radioprotection, cette irradiation recue au niveau du chirurgien et du patient. Materiel et methodes Nous avons inclus prospectivement 100 procedures de FPVP pour lesquelles nous avons releve les doses d’irradiation de l’operateur principal. Pour chaque intervention, les doses du rayonnement absorbees sur le corps entier, les cristallins et les extremites ont ete mesurees. Resultats Nos resultats montrent une dose d’exposition moyenne par procedure sur le corps entier, les extremites et les cristallins qui atteint respectivement, 1,7 ± 2,8 μSv, 204,7 ± 260,9 μSv et 30,5 ± 25,9 μSv. Discussion Selon ses valeurs, l’exposition des extremites et des cristallins du chirurgien depassera la limite annuelle admise par la Commission internationale de protection radiologique (CIPR) apres respectivement 2440 et 4840 procedures. Conclusion Les directives recentes europeennes vont reduire la dose d’exposition oculaire annuelle maximale de 150 a 20 mSv. Le nombre d’interventions chirurgicales pour ne pas atteindre le seuil oculaire, selon nos resultats, ne devra pas depasser 645 procedures par an. Dans l’attente de la democratisation des systemes de neuronavigations, l’utilisation de la fluoroscopie conventionnelle expose les yeux en premier lieu et doivent donc etre protege par des verres plombes. Niveau de preuve IV serie de cas.

Rationale Intravenous administration of stable isotope labeled amino acid ((13)C6-leucine) to humans recently made it possible to study the metabolism of specific biomarkers in cerebrospinal fluid (CSF) using targeted mass spectrometry (MS). This labeling approach could be of great interest for monitoring many leucine-containing peptides in parallel, using high-resolution MS. This will make it possible to quantify the rates of synthesis and clearance of a large range of proteins in humans with a view to obtaining new insights into protein metabolism processes and the pathophysiology of diseases such as Alzheimer's disease. Methods Proteins from human lumbar and ventricular CSF samples collected at different times after intravenous (13)C6-leucine infusion were digested enzymatically with LysC/trypsin after being denatured, reduced and alkylated. Desalted tryptic peptides were fractionated using Strong Cation eXchange chromatography (SCX) and analyzed using nanoflow liquid chromatography (nano-LC) coupled to a QTOF Impact II (Bruker Daltonics) mass spectrometer. Data-dependent acquisition (DDA) mode was used to identify and quantify light and heavy (13)C6-leucine peptides. The ratios of (13)C6-leucine incorporation were calculated using the Skyline software program in order to determine the rates of appearance and clearance of proteins in the CSF. Results After SCX fractionation and quadrupole time-of-flight (QTOF) analysis, 4528 peptides containing leucine were identified in five fractions prepared from 40 μL of CSF. Upon analyzing one of these fractions, 66 peptides (2.7%) corresponding to 61 individual proteins had significant and reproducible rate of (13)C6-leucine incorporation at various time points. The plots of the light-to-heavy peptide ratios showed the existence of proteins with different patterns of appearance and clearance in the CSF. Conclusions The Stable Isotope Labeling Amino acid in Vivo (SILAV) method presented here, which yields unprecedented information about protein metabolism in humans, constitutes a promising new approach which certainly holds great potential in the field of clinical proteomics.

BACKGROUND Hidden by the perisylvian operculi, insular cortex has long been underexplored in the context of epilepsy surgery. Recent studies advocated stereoelectroencephalography (SEEG) as a reliable tool to explore insular cortex and its involvement in intractable epilepsy and suggested that insular seizures could be an underestimated entity. However, the results of insular resection to treat pharmacoresistant epilepsy are rarely reported. OBJECTIVE We report 6 consecutive cases of right insular resection performed based on anatomoelectroclinical correlations provided by SEEG. METHODS Six right-handed patients (3 male, 3 female) with drug-resistant epilepsy underwent comprehensive presurgical evaluation. Based on video electroencephalographic recordings, they all underwent SEEG evaluation with bilateral (n = 4) or unilateral right (n = 2) insular depth electrode placement. All patients had both orthogonal and oblique (1 anterior, 1 posterior) insular electrodes (n = 4-6 electrodes). Preoperative magnetic resonance imaging findings were normal in 4 patients, 1 patient had right insular focal cortical dysplasia, and 1 patient had a right opercular postoperative scar (cavernous angioma). All patients underwent right partial insular corticectomy via the subpial transopercular approach. RESULTS Intracerebral recordings demonstrated an epileptogenic zone confined to the right insula in all patients. After selective insular resection, 5 of 6 patients were seizure free (Engel class I) with a mean follow-up of 36.2 months (range, 18-68 months). Histological findings revealed focal cortical dysplasia in 5 patients and a gliosis scar in 1 patient. All patients had minor transient neurological deficit (eg, facial paresis, dysarthria). CONCLUSION Insular resection based on SEEG findings can be performed safely with a significant chance of seizure freedom. ABBREVIATIONS EEG, electroencephalographyEZ, epileptic zoneFCD, focal cortical dysplasiaILE, insular lobe epilepsySEEG, stereoelectroencephalography.

International audience; PURPOSE:We report on a 72-year-old male patient who developed a nontraumatic spinal subdural hematoma (SSDH) during rivaroxaban therapy, a relatively new orally administered direct factor Xa inhibitor.CASE DESCRIPTION:The patient sustained a sudden onset of interscapular pain, followed by gait impairment and paraplegia. Magnetic resonance imaging (MRI) of the spine demonstrated SSDH from T6 to T8. Laboratory tests revealed a high rivaroxaban level, associated with a major hemorrhagic risk. Surgery was, therefore, performed the following morning, after normalization of coagulation parameters.CONCLUSION:Determining the time of safe surgery remains challenging when hemorrhagic complications happen with direct factor Xa inhibitor, especially when neurological prognosis is engaged. Spinal subdural hematoma has not previously been reported following rivaroxaban therapy.

Object Preservation of the visual field in glioma surgery, especially avoidance of hemianopia, is crucial for patients' quality of life, particularly for driving. Recent studies used tractography or cortical occipital stimulation to try to avoid visual deficit. However, optic radiations have not been directly mapped intraoperatively. The authors present, for the first time to their knowledge, a consecutive series of awake surgeries for cerebral glioma with intrasurgical identification and preservation of visual pathways using subcortical electrical mapping. Methods Fourteen patients underwent awake resection of a glioma (1 WHO Grade I, 11 WHO Grade II, 2 WHO Grade III) involving the optic radiations. The patients had no presurgical visual field deficit. Intraoperatively, a picture-naming task was used, with presentation of 2 objects situated diagonally on a screen divided into 4 quadrants. An image was presented in the quadrant to be saved and another image was presented in the opposite quadrant. Direct subcortical electrostimulation was repeatedly performed without the patient's knowledge, until optic radiations were identified (transient visual disturbances). All patients underwent an objective visual field assessment 3 months after surgery. Results All patients experienced visual symptoms during stimulation. These disturbances led the authors to stop the tumor resection at that level. Postoperatively, only 1 patient had a permanent hemianopia, despite an expected quadrantanopia in 12 cases. The mean extent of resection was 93.6% (range 85%–100%). Conclusions Online identification of optic radiations by direct subcortical electrostimulation is a reliable and effective method to avoid permanent hemianopia in surgery for gliomas involving visual pathways.

Intravenous administration of stable isotope labeled amino acid ((13)C6-leucine) to humans recently made it possible to study the metabolism of specific biomarkers in cerebrospinal fluid (CSF) using targeted mass spectrometry (MS). This labeling approach could be of great interest for monitoring many leucine-containing peptides in parallel, using high-resolution MS. This will make it possible to quantify the rates of synthesis and clearance of a large range of proteins in humans with a view to obtaining new insights into protein metabolism processes and the pathophysiology of diseases such as Alzheimer's disease.Proteins from human lumbar and ventricular CSF samples collected at different times after intravenous (13)C6-leucine infusion were digested enzymatically with LysC/trypsin after being denatured, reduced and alkylated. Desalted tryptic peptides were fractionated using Strong Cation eXchange chromatography (SCX) and analyzed using nanoflow liquid chromatography (nano-LC) coupled to a QTOF Impact II (Bruker Daltonics) mass spectrometer. Data-dependent acquisition (DDA) mode was used to identify and quantify light and heavy (13)C6-leucine peptides. The ratios of (13)C6-leucine incorporation were calculated using the Skyline software program in order to determine the rates of appearance and clearance of proteins in the CSF.After SCX fractionation and quadrupole time-of-flight (QTOF) analysis, 4528 peptides containing leucine were identified in five fractions prepared from 40 μL of CSF. Upon analyzing one of these fractions, 66 peptides (2.7%) corresponding to 61 individual proteins had significant and reproducible rate of (13)C6-leucine incorporation at various time points. The plots of the light-to-heavy peptide ratios showed the existence of proteins with different patterns of appearance and clearance in the CSF.The Stable Isotope Labeling Amino acid in Vivo (SILAV) method presented here, which yields unprecedented information about protein metabolism in humans, constitutes a promising new approach which certainly holds great potential in the field of clinical proteomics.

Preservation of the visual field in glioma surgery, especially avoidance of hemianopia, is crucial for patients' quality of life, particularly for driving. Recent studies used tractography or cortical occipital stimulation to try to avoid visual deficit. However, optic radiations have not been directly mapped intraoperatively. The authors present, for the first time to their knowledge, a consecutive series of awake surgeries for cerebral glioma with intrasurgical identification and preservation of visual pathways using subcortical electrical mapping.Fourteen patients underwent awake resection of a glioma (1 WHO Grade I, 11 WHO Grade II, 2 WHO Grade III) involving the optic radiations. The patients had no presurgical visual field deficit. Intraoperatively, a picture-naming task was used, with presentation of 2 objects situated diagonally on a screen divided into 4 quadrants. An image was presented in the quadrant to be saved and another image was presented in the opposite quadrant. Direct subcortical electrostimulation was repeatedly performed without the patient's knowledge, until optic radiations were identified (transient visual disturbances). All patients underwent an objective visual field assessment 3 months after surgery.All patients experienced visual symptoms during stimulation. These disturbances led the authors to stop the tumor resection at that level. Postoperatively, only 1 patient had a permanent hemianopia, despite an expected quadrantanopia in 12 cases. The mean extent of resection was 93.6% (range 85%-100%).Online identification of optic radiations by direct subcortical electrostimulation is a reliable and effective method to avoid permanent hemianopia in surgery for gliomas involving visual pathways.

We report a 33-year-old man with a history of chronic cannabis use who sustained myocardial infarction followed by cerebral infarction after a recent significant increase in cannabis use. This is the first case of cannabis-associated stroke of probable cardioembolic origin.

Importance There is an increasing interest in BRAF V600 mutations in melanomas and their associated sensitivity to vemurafenib, a BRAF inhibitor. However, physicians cannot find information in the literature about vemurafenib response for rare and/or atypical BRAF mutations. Observations We describe the identification of a novel complex BRAF mutation associated with major clinical response to vemurafenib in a patient with metastatic melanoma. Using a pyrosequencing method, we determined that the tumor positive for mutated BRAF, uncovering a novel c.1799_1803delinsAT; p.V600-K601>D variant. We uncovered this atypical BRAF mutation with 2 different sequencing methods, both in the primary lesion and in 1 metastasis. The patient was immediately treated with vemurafenib as monotherapy and achieved a prolonged (5.5-month) positive response. Conclusions and Relevance We analyzed the consequences of the BRAF V600-K601>D mutation in terms of amino acids. We referred to the published data and databases to screen chemical properties of well-known BRAF V600 mutations and other complex BRAF mutations to find common features of activated BRAF mutations. Importantly, we highlighted that both the site of the mutation and the involved amino acids are important to predict vemurafenib response. Our conclusion is that complex BRAF mutation surrounding codon 600 could also be sensitive to BRAF inhibitors. .