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1.
Rev Neurol (Paris) ; 179(5): 437-448, 2023 Jun.
Article in English | MEDLINE | ID: mdl-36907710

ABSTRACT

For decades, diffuse glioma (DG) studies mostly focused on oncological considerations, whereas functional outcomes received less attention. Currently, because overall survival has increased in DG, especially in low-grade glioma (overall survival > 15 years), quality of life including neurocognitive and behavioral aspects should be assessed and preserved more systematically, particularly regarding surgery. Indeed, early maximal tumor removal results in greater survival in both high-grade and low-grade gliomas, leading to propose "supra-marginal" resection, with excision of the peritumoral zone in diffuse neoplasms. To minimize functional risks while maximizing the extent of resection, traditional "tumor-mass resection" is replaced by "connectome-guided resection" conducted under awake mapping, taking into account inter-individual brain anatomo-functional variability. A better understanding of the dynamic interplay between DG progression and reactional neuroplastic mechanisms is critical to adapt a personalized multistage therapeutic strategy, with integration of functional neurooncological (re)operation(s) in a multimodal management scheme including repeated medical therapies. Because the therapeutic armamentarium remains limited, the aims of this paradigmatic shift are to predict one/several step(s) ahead glioma behavior, its modifications, and compensatory neural networks reconfiguration over time in order to optimize the onco-functional benefit of each treatment - either in isolation or in combination with others - in human beings bearing a chronic tumoral disease while enjoying an active familial and socio-professional life as close as possible to their expectations. Thus, new ecological endpoints such as return to work should be incorporated into future DG trials. "Preventive neurooncology" might also be envisioned, by proposing a screening policy to discover and treat incidental glioma earlier.


Subject(s)
Brain Neoplasms , Glioma , Neurosurgery , Humans , Brain Neoplasms/surgery , Brain Neoplasms/pathology , Quality of Life , Glioma/surgery , Glioma/pathology , Neurosurgical Procedures/methods
2.
Anal Chem ; 94(35): 11967-11972, 2022 09 06.
Article in English | MEDLINE | ID: mdl-35998076

ABSTRACT

One of the main challenges in cancer management relates to the discovery of reliable biomarkers, which could guide decision-making and predict treatment outcome. In particular, the rise and democratization of high-throughput molecular profiling technologies bolstered the discovery of "biomarker signatures" that could maximize the prediction performance. Such an approach was largely employed from diverse OMICs data (i.e., genomics, transcriptomics, proteomics, metabolomics) but not from epitranscriptomics, which encompasses more than 100 biochemical modifications driving the post-transcriptional fate of RNA: stability, splicing, storage, and translation. We and others have studied chemical marks in isolation and associated them with cancer evolution, adaptation, as well as the response to conventional therapy. In this study, we have designed a unique pipeline combining multiplex analysis of the epitranscriptomic landscape by high-performance liquid chromatography coupled to tandem mass spectrometry with statistical multivariate analysis and machine learning approaches in order to identify biomarker signatures that could guide precision medicine and improve disease diagnosis. We applied this approach to analyze a cohort of adult diffuse glioma patients and demonstrate the existence of an "epitranscriptomics-based signature" that permits glioma grades to be discriminated and predicted with unmet accuracy. This study demonstrates that epitranscriptomics (co)evolves along cancer progression and opens new prospects in the field of omics molecular profiling and personalized medicine.


Subject(s)
Glioma , RNA , Biomarkers , Glioma/diagnosis , Glioma/genetics , Humans , Metabolomics/methods , Multivariate Analysis , Proteomics/methods
3.
Rev Neurol (Paris) ; 177(9): 1093-1103, 2021 Nov.
Article in English | MEDLINE | ID: mdl-34563375

ABSTRACT

Although clinical neurology was mainly erected on the dogma of localizationism, numerous reports have described functional recovery after lesions involving presumed non-compensable areas in an inflexible view of brain processing. Here, the purpose is to review new insights into the functional connectome and the mechanisms underpinning neural plasticity, gained from intraoperative direct electrostimulation mapping and real-time behavioral monitoring in awake patients, combined with perioperative neuropsychological and neuroimaging data. Such longitudinal anatomo-functional correlations resulted in the reappraisal of classical models of cognition, especially by highlighting the dynamic interplay within and between neural circuits, leading to the concept of meta-network (network of networks), as well as by emphasizing that subcortical connectivity is the main limitation of neuroplastic potential. Beyond their contribution to basic neurosciences, these findings might also be helpful for an optimization of care for brain-damaged patients, such as in resective oncological or epilepsy neurosurgery in structures traditionally deemed inoperable (e.g., in Broca's area) as well as for elaborating new programs of functional rehabilitation, eventually combined with transcranial brain stimulation, aiming to change the connectivity patterns in order to enhance cognitive competences following cerebral injury.


Subject(s)
Brain Neoplasms , Connectome , Brain/diagnostic imaging , Brain/surgery , Brain Neoplasms/complications , Brain Neoplasms/diagnostic imaging , Brain Neoplasms/surgery , Humans , Neuronal Plasticity , Neurosurgical Procedures , Wakefulness
4.
Sci Rep ; 10(1): 5504, 2020 03 26.
Article in English | MEDLINE | ID: mdl-32218467

ABSTRACT

IDH1-mutated gliomas are slow-growing brain tumours which progress into high-grade gliomas. The early molecular events causing this progression are ill-defined. Previous studies revealed that 20% of these tumours already have transformation foci. These foci offer opportunities to better understand malignant progression. We used immunohistochemistry and high throughput RNA profiling to characterize foci cells. These have higher pSTAT3 staining revealing activation of JAK/STAT signaling. They downregulate RNAs involved in Wnt signaling (DAAM2, SFRP2), EGFR signaling (MLC1), cytoskeleton and cell-cell communication (EZR, GJA1). In addition, foci cells show reduced levels of RNA coding for Ethanolamine-Phosphate Phospho-Lyase (ETNPPL/AGXT2L1), a lipid metabolism enzyme. ETNPPL is involved in the catabolism of phosphoethanolamine implicated in membrane synthesis. We detected ETNPPL protein in glioma cells as well as in astrocytes in the human brain. Its nuclear localization suggests additional roles for this enzyme. ETNPPL expression is inversely correlated to glioma grade and we found no ETNPPL protein in glioblastomas. Overexpression of ETNPPL reduces the growth of glioma stem cells indicating that this enzyme opposes gliomagenesis. Collectively, these results suggest that a combined alteration in membrane lipid metabolism and STAT3 pathway promotes IDH1-mutated glioma malignant progression.


Subject(s)
Brain Neoplasms/genetics , Brain Neoplasms/metabolism , Carbon-Oxygen Lyases/genetics , Glioma/genetics , Glioma/metabolism , Isocitrate Dehydrogenase/genetics , STAT3 Transcription Factor/metabolism , Brain Neoplasms/pathology , Cell Line, Tumor , Cell Proliferation , Cell Transformation, Neoplastic/genetics , Cell Transformation, Neoplastic/metabolism , Cell Transformation, Neoplastic/pathology , Disease Progression , Down-Regulation , Gene Expression Profiling , Glioma/pathology , Humans , Immunohistochemistry , Lipid Metabolism , Mutation , Phosphorylation , Signal Transduction
5.
J Neural Eng ; 17(1): 016047, 2020 02 05.
Article in English | MEDLINE | ID: mdl-31778987

ABSTRACT

OBJECTIVE: Direct electrical stimulation (DES) at 60 Hz is used to perform real-time functional mapping of the brain, and guide tumour resection during awake neurosurgery. Nonetheless, the electrophysiological effects of DES remain largely unknown, both locally and remotely. APPROACH: In this study, we lowered the DES frequency to 1-10 Hz and we used a differential recording mode of electro-corticographic (ECoG) signals to improve the focality with a simple algorithm to remove the artefacts due to the response of the acquisition chain. MAIN RESULTS: Doing so, we were able to observe different components in the evoked potentials triggered by simulating the cortex or the subcortical white matter pathways near the recording electrodes and by stimulating the cortex remotely from the recording site. More particularly, P0 and N1 components were repeatedly observed on raw ECoG signals without the need to average the data. SIGNIFICANCE: This new methodology is important to probe the electrophysiological states and the connectivity of the brain in vivo and in real time, namely to perform electrophysiological brain mapping on human patients operated in the neurosurgical room and to better understand the electrophysiological spreading of DES.


Subject(s)
Action Potentials/physiology , Brain Mapping/methods , Brain/physiology , Electrocorticography/methods , Neurosurgical Procedures/methods , Wakefulness/physiology , Brain/surgery , Brain Mapping/instrumentation , Humans , Stereotaxic Techniques
6.
Neuroimage Clin ; 24: 102010, 2019.
Article in English | MEDLINE | ID: mdl-31734532

ABSTRACT

The dynamic connectome perspective states that brain functions arise from the functional integration of distributed and/or partly overlapping networks. Diffuse low-grade gliomas (DLGG) have a slow infiltrating character. Here we addressed whether and how anatomical disconnection following DLGG growth and resection might interfere with functional resting-state connectivity, specifically in relation to picture naming. Thirty-nine native French persons with a left DLGG were included. All underwent awake surgical resection of the tumor using direct brain electrostimulation to preserve critical eloquent regions. The anatomical disconnectivity risk following the DLGG volume and the resection, and the functional connectivity of resting-state fMRI images in relation to picture naming were evaluated prior to and three months after surgery. Resting-state connectivity patterns were compared with nineteen healthy controls. It was demonstrated that picture naming was strongly dependent on the semantic network that emerged from the integration and interaction of regions within multiple resting-state brain networks, in which their specific role could be explained in the light of the broader resting-state network they take part in. It emphasized the importance of a whole brain approach with specific clinical data input, during resting-state analysis in case of lesion. Adaptive plasticity was found in secondary regions, functionally connected to regions close to the tumor and/or cavity, marked by an increased connectivity of the right and left inferior parietal lobule with the left inferior temporal gyrus. In addition, an important role was identified for the superior parietal lobe, connected with the frontal operculum, suggesting functional compensation by means of attentional resources in order to name a picture via recruitment of the frontoparietal attention network.


Subject(s)
Brain Neoplasms , Cerebral Cortex/physiopathology , Connectome , Glioma , Nerve Net/physiopathology , Neuronal Plasticity/physiology , Pattern Recognition, Visual/physiology , Adult , Brain Neoplasms/diagnostic imaging , Brain Neoplasms/pathology , Brain Neoplasms/surgery , Cerebral Cortex/diagnostic imaging , Female , Glioma/diagnostic imaging , Glioma/pathology , Glioma/surgery , Humans , Male , Middle Aged , Nerve Net/diagnostic imaging , Neurosurgical Procedures
7.
Glia ; 66(2): 239-255, 2018 02.
Article in English | MEDLINE | ID: mdl-29027701

ABSTRACT

Diffuse low grade gliomas (DLGG, grade II gliomas) are slowly-growing brain tumors that often progress into high grade gliomas. Most tumors have a missense mutation for IDH1 combined with 1p19q codeletion in oligodendrogliomas or ATRX/TP53 mutations in astrocytomas. The phenotype of tumoral cells, their environment and the pathways activated in these tumors are still ill-defined and are mainly based on genomics and transcriptomics analysis. Here we used freshly-resected tumors to accurately characterize the tumoral cell population and their environment. In oligodendrogliomas, cells express the transcription factors MYT1, Nkx2.2, Olig1, Olig2, Sox8, four receptors (EGFR, PDGFRα, LIFR, PTPRZ1) but not the co-receptor NG2 known to be expressed by oligodendrocyte progenitor cells. A variable fraction of cells also express the more mature oligodendrocytic markers NOGO-A and MAG. DLGG cells are also stained for the young-neuron marker doublecortin (Dcx) which is also observed in oligodendrocytic cells in nontumoral human brain. In astrocytomas, MYT1, PDGFRα, PTPRZ1 were less expressed whereas Sox9 was prominent over Sox8. The phenotype of DLGG cells is overall maintained in culture. Phospho-array screening showed the absence of EGFR and PDGFRα phosphorylation in DLGG but revealed the strong activation of p44/42 MAPK/ERK which was present in a fraction of tumoral cells but also in nontumoral cells. These results provide evidence for the existence of close relationships between the cellular phenotype and the mutations found in DLGG. The slow proliferation of these tumors may be associated with the absence of activation of PDGFRα/EGFR receptors.


Subject(s)
Brain Neoplasms/genetics , ErbB Receptors/genetics , Glioma/genetics , Isocitrate Dehydrogenase/genetics , Mutation/genetics , Receptor, Platelet-Derived Growth Factor alpha/genetics , Adult , Animals , Biomarkers, Tumor/genetics , Biomarkers, Tumor/metabolism , Brain Neoplasms/metabolism , Brain Neoplasms/pathology , Doublecortin Protein , ErbB Receptors/metabolism , Female , Glioma/metabolism , Glioma/pathology , Homeobox Protein Nkx-2.2 , Homeodomain Proteins , Humans , Isocitrate Dehydrogenase/metabolism , Male , Mice , Middle Aged , Neoplasm Grading/methods , Nuclear Proteins , Receptor, Platelet-Derived Growth Factor alpha/metabolism , Transcription Factors , Tumor Cells, Cultured , Young Adult
8.
Neurochirurgie ; 63(3): 219-226, 2017 Jun.
Article in English | MEDLINE | ID: mdl-28502568

ABSTRACT

INTRODUCTION: Surgical resection of supratentorial cavernous angiomas located in eloquent areas poses a significant risk to the patient of postoperative neurological impairment and justifies intraoperative functional monitoring. METHODS: Multicentre retrospective series of adult patients with cavernous angiomas located within eloquent areas and treated with functional-based surgical resection according to functional boundaries under intraoperative functional cortico-subcortical monitoring under awake conditions. RESULTS: Fifty patients (18 males, mean 36.3±10.8 year-old) underwent surgical resection with intraoperative cortico-subcortical functional mapping using direct electrostimulation under awake conditions for a cavernous angioma located in eloquent areas with a mean postoperative follow-up of 21.0±21.2 months. At presentation, the cavernous angioma had previously resulted in severe impairment (neurological deficit in 34%, seizures in 70%, uncontrolled seizures in 34%, reduced Karnofsky Performance Status score of 70 or less in 24%, inability to work in 52%). Functional-based surgical resection allowed complete removal of the cavernous angioma in 98% and of the haemosiderin rim in 82%. Postoperative seizures and other complications were rare, and similarly so across all centres included in this series. Postoperatively, we found functional improvement in 84% of patients (reduced Karnofsky Performance Status score of 70 or less in 6%, uncontrolled seizures in 16%, and inability to work in 11%). CONCLUSION: Functional-based surgical resection aids the safe and complete resection of cavernous angiomas located in eloquent areas while minimizing the surgical risks. Functional mapping has to be considered in such challenging cases.


Subject(s)
Brain Neoplasms/surgery , Hemangioma, Cavernous/surgery , Neurosurgical Procedures , Wakefulness/physiology , Adult , Aged , Brain Mapping/methods , Electric Stimulation/methods , Female , Humans , Intraoperative Neurophysiological Monitoring , Male , Middle Aged , Neuronavigation/methods , Neurosurgical Procedures/methods , Retrospective Studies
9.
Neurochirurgie ; 63(3): 259-265, 2017 Jun.
Article in English | MEDLINE | ID: mdl-28522182

ABSTRACT

BACKGROUND AND PURPOSE: The historical approach in neurooncology is used to mainly investigate the tumor, with very few considerations regarding the brain itself. Nonetheless, to select the best personalized therapeutic management for each patient with a diffuse glioma, i.e. to optimize the "onco-functional balance", the brain reaction induced by glioma growth and migration should be studied. Indeed, due to strong interactions between the glioma and the brain, cerebral adaptive phenomena often occur in order to maintain neurological and cognitive functions, as well as to compensate glioma spreading. Here, the goal is to detail mechanisms underlying neuroplasticity and its implications for surgical neurooncology. METHODS: Data issues from cerebral mapping and functional outcomes in patients who underwent awake surgery for gliomas were discussed. RESULTS: Massive resections of the brain, including so-called "eloquent areas", are possible without generating permanent neurological deficits in adult patients harbouring a diffuse glioma. CONCLUSION: From a fundamental point of view, these findings open the door to a hodotopical anatomo-functional organization of the brain, i.e. organized in dynamic and interactive parallel large-scale distributed networks, able to compensate for each other. Furthermore, cognitive neurosciences represent valuable help to neuro-oncology, by leading to the elaboration of new treatment strategies, such as multistage surgical approach, made possible thanks to cerebral remapping over years. In other words, understanding neuroplasticity in a connectomal account of brain processing permitted a dramatic improvement of both quality of life as well as overall survival in glioma patients, and resulted in the proposal of an "individualized functional neurooncology".


Subject(s)
Brain Neoplasms/surgery , Glioma/surgery , Quality of Life , Wakefulness/physiology , Brain/surgery , Brain Mapping/methods , Brain Neoplasms/pathology , Brain Neoplasms/physiopathology , Glioma/pathology , Glioma/physiopathology , Humans , Neuronal Plasticity/physiology , Neurosurgical Procedures/methods
10.
Neurochirurgie ; 63(5): 381-390, 2017 Nov.
Article in French | MEDLINE | ID: mdl-28527519

ABSTRACT

OBJECTIVES: Intramedullary gliomas are rare tumors accounting for less than 4% of all primary central nervous system tumors. The aims of this retrospective multicenter study were to assess their natural outcome as well as management. METHODS AND MATERIALS: We studied 332 patients from 1984 to 2011. Histopathological examination revealed 72% ependymomas (94% were low grade tumors), 24% astrocytomas (29% were high grade tumors), 2.4% mixed gliomas and 1.7% oligodendrogliomas. RESULTS: The mean age at diagnosis was 42.4 years for ependymomas, with male predominance, versus 39.6 years for astrocytomas. Pain was the most common initial presentation. In 20% of cases, astrocytomas were biopsied alone, but more than 80% of ependymomas had surgical resection. Radiotherapy and chemotherapy were reserved for malignant tumors, especially if they were ependymomas. The 5-year survival rate was 76.8% for astrocytomas and 94.5% for ependymomas. Histology, functional status prior to surgery, and tumor grade are among the prognostic factors. CONCLUSION: Our study showed that surgical treatment of gliomas is well codified, at least for ependymomas, but adjuvant treatment continues to play a marginal role in the management even in astrocytomas, which are infiltrative tumors.


Subject(s)
Glioma/therapy , Spinal Cord Neoplasms/therapy , Adult , Female , Glioma/diagnosis , Glioma/pathology , Humans , Male , Retrospective Studies , Spinal Cord Neoplasms/diagnosis , Spinal Cord Neoplasms/pathology
11.
Neurochirurgie ; 63(3): 250-258, 2017 Jun.
Article in English | MEDLINE | ID: mdl-28161011

ABSTRACT

OBJECTIVE: Incidentally discovered diffuse low-grade gliomas progress in a fashion similar to their symptomatic counterparts. Their early detection allows more effective pre-emptive and individualized oncological treatment. We assessed the safety and efficacy of maximal safe resection according to functional boundaries for incidental diffuse low-grade gliomas in eloquent areas. MATERIAL AND METHODS: Two-centre retrospective series of adult patients with incidental diffuse low-grade gliomas located within/close to eloquent areas in the dominant hemisphere, treated with maximal surgical resection according to functional boundaries under intraoperative functional cortico-subcortical monitoring under awake conditions, and with a minimal follow-up of 24months. RESULTS: The series included 19 patients (8 men, 11 women) with no preoperative neurological deficit but with a radiologically enlarged glioma. No intraoperative seizure, postoperative infection, haematoma or wound-healing problem was observed. In the immediate postsurgical period, a transient neurological worsening occurred in 10 patients. The resection (mean rate 96.4%; range, 82.4-100) was supratotal in 5 cases, total in 5 cases, subtotal in 7 cases, and partial in 2 cases. Six months after surgery, all patients recovered after functional rehabilitation, with no permanent neurological deficit, Karnofsky Performance Status was 100 (except for one patient who received early postoperative radiotherapy) and no seizures were observed. The survival without progression requiring oncological treatment was significantly longer in patients with a total/supratotal resection than in patients with a partial/subtotal resection. CONCLUSIONS: These results suggest the reproducibility, safety, and effectiveness of an early maximal functionally based resection within cortico-subcortical functional boundaries for incidental diffuse low-grade gliomas in adults in centres hyperspecialized in surgical neuro-oncology.


Subject(s)
Brain Neoplasms/surgery , Epilepsy/surgery , Glioma/surgery , Adult , Brain/surgery , Brain Mapping/methods , Brain Neoplasms/complications , Brain Neoplasms/diagnosis , Electric Stimulation/methods , Epilepsy/etiology , Female , Glioma/complications , Glioma/diagnosis , Humans , Intraoperative Neurophysiological Monitoring , Male , Middle Aged , Neurosurgical Procedures/methods , Postoperative Complications/prevention & control , Retrospective Studies , Treatment Outcome , Wakefulness/physiology
12.
Neurochirurgie ; 63(3): 235-242, 2017 Jun.
Article in English | MEDLINE | ID: mdl-28161012

ABSTRACT

INTRODUCTION: Surgical resection in premotor areas can lead to supplementary motor area syndrome as well as a permanent deficit. However, recent findings suggest a putative role of the negative motor network in those dysfunctions. Our objective was to compare the functional results in two groups of adult patients who underwent the resection of a frontal glioma with and without resection of the negative motor networks. MATERIAL AND METHODS: Twelve patients (total of 13 surgeries) were selected for awake surgery for a frontal glioma. Negative motor responses were monitored during surgery at the cortical and subcortical levels. Sites eliciting negative motor responses were first identified then spared (n=8) or removed (n=5) upon oncological requirements. RESULTS: In the group with removal of the negative motor network (n=5), all patients presented a complete supplementary motor area syndrome with akinesia and mutism. At 3months, they all presented bimanual coordination dysfunction and fine movement disorders. In the group with preservation of the negative motor network (n=8), all patients presented transient and slight disorders of speech or upper limb, they all recovered completely at 3months. DISCUSSION: The negative motor network is a part of a modulatory motor network involved in the occurrence of the supplementary motor area syndrome and the permanent deficit after resection in premotor areas. Then, intraoperative functional cortico-subcortical mapping using direct electrostimulation under awake surgery seems mandatory to avoid deficit in bimanual coordination and fine movements during surgery in premotor areas.


Subject(s)
Brain Mapping , Brain Neoplasms/surgery , Glioma/surgery , Intraoperative Neurophysiological Monitoring , Wakefulness/physiology , Adult , Craniotomy/methods , Electric Stimulation/methods , Female , Humans , Male , Middle Aged , Neural Pathways/physiopathology , Neural Pathways/surgery
13.
Neurochirurgie ; 63(3): 243-249, 2017 Jun.
Article in English | MEDLINE | ID: mdl-28185647

ABSTRACT

Successful management of diffuse low-grade and high-grade gliomas in adults is a challenge for neuro-oncologists. Indeed, due to their highly infiltrative feature, these diseases remain incurable despite therapeutic advances. Nevertheless, the elaboration of individualized therapeutic strategies has led to an improvement of both overall survival and quality of life. In particular, the impact of surgical resection on diffuse glioma survival has been extensively demonstrated. However, this impact is significant only when the resection is total (i.e., complete removal of the T2-hyperintensity in diffuse low-grade gliomas, or complete removal of the enhancement in high-grade gliomas), or at least subtotal. Interestingly, biopsy samples within and beyond the abnormalities, defined by magnetic resonance imaging, have shown that the actual spatial extent of gliomas was underestimated by this conventional imaging modality, since glioma cells were present outside the signal abnormalities. Thus, it was suggested that the removal of a margin around the tumor visible on magnetic resonance imaging, i.e. "supratotal resection", might improve the outcomes in diffuse gliomas. To achieve this type of supramaximal resection, while preserving the quality of life, a new concept is to switch from an image-guided surgery to a functional-guided surgery, i.e. to pursue the resection up to the eloquent neural networks using intraoperative direct electrical stimulation mapping in awake patients. The aim of this article was to review the recent data about supratotal resection, including both oncological and functional results. Favorable outcomes have recently opened the door to the principle of "preventive surgery" in incidentally discovered gliomas, and to the proposal of a medical screening.


Subject(s)
Brain Neoplasms/surgery , Glioma/surgery , Neurosurgical Procedures , Wakefulness/physiology , Brain Neoplasms/pathology , Glioma/pathology , Humans , Intraoperative Neurophysiological Monitoring , Neurosurgical Procedures/methods , Quality of Life , Surgery, Computer-Assisted/methods
15.
J Neurosurg Sci ; 59(4): 361-71, 2015 Dec.
Article in English | MEDLINE | ID: mdl-25907410

ABSTRACT

The traditional dilemma making surgery for diffuse low-grade gliomas (DLGGs) challenging is underlain by the need to optimize tumor resection in order to significantly increase survival versus the risk of permanent neurological morbidity. Development of neuroimaging led neurosurgeons to achieve tumorectomy according to the oncological limits provided by preoperative or intraoperative structural and metabolic imaging. However, this principle is not coherent, neither with the infiltrative nature of DLGGs nor with the limited resolution of current neuroimaging. Indeed, despite technical advances, MRI still underestimates the actual spatial extent of gliomas, since tumoral cells are present several millimeters to centimeters beyond the area of signal abnormalities. Furthermore, cortical and subcortical structures may be still crucial for brain functions despite their invasion by this diffuse tumoral disease. Finally, the lack of reliability of functional MRI has also been demonstrated. Therefore, to talk about "maximal safe resection" based upon neuroimaging is a non-sense, because oncological MRI does not show the tumor and functional MRI does not show critical neural pathways. This review proposes an original concept in neuro-oncological surgery, i.e. to resect DLGG to the boundaries of brain functions, thanks to intraoperative electrical mapping performed in awake patients. This paradigmatic shift from image-guided resection to functional mapping-guided resection, based upon an accurate study of brain connectomics and neuroplasticity in each patient throughout tumor removal has permitted to solve the classical dilemma, by increasing both survival and quality of life in DLGG patients. With this in mind, brain surgeons should also be neuroscientists.


Subject(s)
Brain Mapping/methods , Brain Neoplasms/surgery , Glioma/surgery , Intraoperative Neurophysiological Monitoring/methods , Neurosurgical Procedures/methods , Humans , Medical Oncology/methods , Medical Oncology/trends , Neurology/methods , Neurology/trends
16.
Neurochirurgie ; 61(1): 46-9, 2015 Feb.
Article in English | MEDLINE | ID: mdl-25595594

ABSTRACT

We report on a young woman with a left temporal diffuse low-grade glioma treated initially by a subtotal resection. A focal anaplastic area appeared 5years later and was treated by radiosurgery. A long-time stabilization was therefore obtained and lasted even after pregnancy, which is a known factor of faster tumour progression. This report shows that radiosurgery could be an option in the multimodal treatment of a selected group of patients with focal malignant transformation of diffuse low-grade glioma. It could permit long-term stabilization of the tumour without any other adjuvant treatment and without compromising the quality of life.


Subject(s)
Brain Neoplasms/surgery , Carcinoma/surgery , Oligodendroglioma/surgery , Radiosurgery/methods , Adolescent , Anticonvulsants , Female , Humans , Magnetic Resonance Imaging , Pregnancy , Seizures/drug therapy , Seizures/etiology , Survivors , Treatment Outcome
17.
J Neurosurg Sci ; 58(4): 199-213, 2014 Dec.
Article in English | MEDLINE | ID: mdl-25418274

ABSTRACT

Awake surgery is not a new technique: this is a new philosophy. Indeed, in surgery for diffuse gliomas performed in awake patients, the goal is not anymore to remove a "tumor mass" according to oncological boundaries (which in essence do not exist in infiltrating neoplasms), but to resect a part of the brain invaded by a chronic tumoral disease, according to functional limits both at cortical and subcortical levels. Therefore, intraoperative electrical mapping is accepted as the gold standard in order to gain information about the functionality of the underlying tissue when performing neuro-oncological surgery. This review should give the reader an overview of principles and indications of mapping of eloquent cortex and subcortical pathways with practical considerations for cerebral tumors. In gliomas, awake mapping has been demonstrated as increasing the surgical indications in so-called "critical areas" with nonetheless a significant decrease of postoperative morbidity­while maximizing the extent of resection. Beyond clinical implications, awake surgery represents a unique opportunity to study neural networks underpinning sensorimotor, visuospatial, language, executive and even behavioral functions in humans. This led to propose new models of connectomics, breaking with the localizationist view of brain processing, and opening the window to the concept of neuroplasticity. In summary, awake mapping enables to make a link between surgical neurooncology and cognitive neurosciences, to improve both survival and quality of life of glioma patients.


Subject(s)
Brain Mapping/methods , Brain Neoplasms/surgery , Connectome/methods , Intraoperative Neurophysiological Monitoring/methods , Neural Pathways/physiology , Wakefulness , Humans , Neurosurgical Procedures/methods
18.
Diagn Interv Imaging ; 95(10): 945-55, 2014 Oct.
Article in English | MEDLINE | ID: mdl-25218490

ABSTRACT

The traditional approach in neuro-oncology is to study the tumor in great detail and ultimately give little consideration to the brain itself. Choosing the best treatment strategy for each patient with a diffuse low-grade glioma, in other words optimizing the oncologic and functional balance, implies not only a full knowledge of the natural history of this chronic disease, but also an understanding of the adaptation of the brain in response to growth and spread of the glioma. The aim of this review is to examine the mechanisms underlying this neuroplasticity, allowing functional compensation when the tumor progresses, and opening the way to new treatments with the principle of shifting towards "functional personalized neuro-oncology", improving both median survival and quality of life.


Subject(s)
Brain Neoplasms/diagnosis , Brain Neoplasms/physiopathology , Glioma/diagnosis , Glioma/physiopathology , Neuronal Plasticity/physiology , Brain/pathology , Brain/physiopathology , Brain Neoplasms/therapy , Disease Progression , Glioma/mortality , Glioma/therapy , Humans , Precision Medicine , Quality of Life , Survival Rate
19.
J Neurosurg Sci ; 2014 May 20.
Article in English | MEDLINE | ID: mdl-24844174

ABSTRACT

Awake surgery is not a new technique: this is a new philosophy. Indeed, in surgery for diffuse gliomas performed in awake patients, the goal is not anymore to remove a "tumor mass" according to oncological boundaries (which in essence do not exist in infiltrating neoplasms), but to resect a part of the brain invaded by a chronic tumoral disease, according to functional limits both at cortical and subcortical levels. Therefore, intraoperative electrical mapping is accepted as the gold standard in order to gain information about the functionality of the underlying tissue when performing neurooncological surgery. This review should give the reader an overview of principles and indications of mapping of eloquent cortex and subcortical pathways with practical considerations for cerebral tumors. In gliomas, awake mapping has been demonstrated as increasing the surgical indications in socalled "critical areas" with nonetheless a significant decrease of postoperative morbidity while maximizing the extent of resection. Beyond clinical implications, awake surgery represents a unique opportunity to study neural networks underpinning sensorimotor, visuospatial, language, executive and even behavioral functions in humans. This led to propose new models of connectomics, breaking with the localisationist view of brain processing, and opening the window to the concept of neuroplasticity. In summary, awake mapping enables to make a link between surgical neurooncology and cognitive neurosciences, to improve both survival and quality of life of glioma patients.

20.
Neurochirurgie ; 59(1): 2-8, 2013 Feb.
Article in English | MEDLINE | ID: mdl-23410764

ABSTRACT

BACKGROUND AND PURPOSE: Surgery for diffuse low-grade glioma (DLGG) was debated for a long time. Discrepancies in the classical literature are mainly due to the lack of objective radiological assessment of the extent of resection (EOR). Here, the goal is to review the recent data on oncological and functional outcomes. METHODS: Surgical series with calculation of EOR on postoperative MRI were reviewed. RESULTS: In all modern series, a more aggressive resection predicted significant improvement in overall survival (OS) compared with a simple debulking. Especially, an extended removal of a margin beyond the MRI-defined abnormalities ("supra-total" resection) significantly increased OS by delaying malignant transformation. Furthermore, advances in intraoperative brain mapping techniques resulted in a minimization of neurological deficits. DISCUSSION/CONCLUSION: These recent data strongly argue in favor of achieving a maximal resection of DLGG as the first therapeutic option. Biopsy should be considered only in very diffuse lesions (gliomatosis) or when a subtotal resection is not a priori possible. Thus, neurosurgeons should change their mind, by operating the brain involved by a chronic tumoral disease rather than by trying to remove a "tumor mass". The aim is not to achieve a simple "tumorectomy", but the most extensive resection of the brain invaded by DLGG, on the condition that this part of the brain is not crucial for cerebral functions. This new philosophy suggests to perform early and maximal resection according to functional (and not purely oncological or anatomical) boundaries in awake patients. This perspective is the best way to build a personalized "functional surgical neuro-oncology".


Subject(s)
Brain Neoplasms/surgery , Glioma/surgery , Neurosurgical Procedures/trends , Astrocytoma/pathology , Astrocytoma/surgery , Biopsy , Brain Mapping , Brain Neoplasms/pathology , Disease Management , Electrodiagnosis , Glioma/pathology , Humans , Magnetic Resonance Imaging , Meta-Analysis as Topic , Monitoring, Intraoperative , Neoplasm Grading , Neoplasm Invasiveness , Neoplasm Recurrence, Local/prevention & control , Neoplasm, Residual , Neoplasms, Neuroepithelial/pathology , Neoplasms, Neuroepithelial/surgery , Neurosurgical Procedures/methods , Practice Guidelines as Topic , Reoperation , Survival Analysis , Treatment Outcome , Wakefulness
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