For many decades, interactions between diffuse lower-grade glioma (LGG) and brain connectome were... more For many decades, interactions between diffuse lower-grade glioma (LGG) and brain connectome were neglected. However, the neoplasm progression is intimately linked to its environment, especially the white matter (WM) tracts and their myelin status. First, while the etiopathogenesis of LGG is unclear, this tumor seems to appear during the adolescence, and it is mostly located within anterior and associative cerebral areas. Because these structures correspond to those which were myelinated later in the brain maturation process, WM myelination could play a role in the development of LGG. Second, WM fibers and the myelin characteristics also participate in LGG diffusion, since glioma cells migrate along the subcortical pathways, especially when exhibiting a demyelinated phenotype, which may result in a large invasion of the parenchyma. Third, such a migratory pattern can induce functional (neurological, cognitive and behavioral) disturbances, because myelinated WM tracts represent the m...
The concept of plasticity describes the mechanisms that rearrange cerebral organization following... more The concept of plasticity describes the mechanisms that rearrange cerebral organization following a brain injury. During the last century, plasticity has beenmainly investigated in humans with acute strokes. It was then shown: (i) that the brain is organized into highly specialized functional areas, often designated ‘eloquent ’ areas and (ii) that a lesion within the eloquent area gives rise tomajor irrevocable deficits. However, in sharp contrast with these observations, it was recently found that patients with low-grade gliomas were able to undergo massive cerebral resections without detectable functional consequence. In this paper, we tackle this puzzling observation and address the idea that brain plasticity cannot be fully understood and fruitfully studied without considering the temporal pattern of the injury inflicted to the brain. To achieve this goal, we first review experimental evidence showing that functional recovery is considerably better in the context of slow-growing...
Diffuse low-grade glioma (DLGG) is a chronic tumoral disease that ineluctably grows, migrates alo... more Diffuse low-grade glioma (DLGG) is a chronic tumoral disease that ineluctably grows, migrates along white matter pathways, and progresses to higher grade of malignancy. Rather than a “wait and watch” policy, a therapeutic attitude is currently the gold standard, with early radical safe surgery as the first treatment. Indeed, intraoperative mapping in awake patients, with maximal resection up to functional boundaries, is significantly associated with a longer overall survival (OS), while preserving or even improving quality of life (QoL). However, most of traditional studies have investigated the impact of only one specific therapy (e.g. impact of surgery, or radiotherapy, or chemotherapy) on OS, without a comprehensive view of the whole management strategy on the patient’s cumulative time with preserved QoL versus time to malignant transformation. Here, our goal is to switch towards a more holistic concept, based on the anticipation of a personalized and long-term multistage therapeutic approach, with on-line adaptation of the strategy over years using feedback issued from clinical, radiological and histomolecular monitoring at the individual level. This dynamic and multistage approach challenges the classical strategy by proposing earlier therapy, by repeating treatments, and by reversing the traditional order of therapies (e.g. neoadjuvant chemotherapy if at least subtotal surgical resection is not possible, no early irradiation), to improve both OS and QoL. Neuro-oncologists should tailor their management strategy during the follow-up on the basis of real-time oncological control and functional outcome. Thus, we propose new personalized strategies dealing with the interactions between the natural course of DLGG, reaction neuroplasticity, and onco-functional modulation induced by serial treatments. The ultimate aim is taking measures to delay malignant transformation as long as possible, while giving DLGG patients a real life that includes planning for their long-term future (e.g. such as deciding whether to have a baby). This philosophy supports an individualized, functional, and preventive neurooncology.
IRECT electrical stimulation (DES) has long been used to perform real-time functional mapping of ... more IRECT electrical stimulation (DES) has long been used to perform real-time functional mapping of the brain. More recently, this technique was introduced in the neurosurgery of slow-growing and infiltrative brain tumors to guide the resection with great success. By generating transient perturbations, this method allows the real-time identification of both cortical areas and subcortical networks that are essential for the function. Thus, as much as possible, non-functional tissue can be removed while minimizing the sequelae. However, the understanding of the electrophysiological effects of DES and, in particular its remote propagation, remains an open and key question. DES can be used to probe on-line and in-vivo the spatio-temporal connectivity and the dynamics of functional networks by associating electrophysiological recordings. Such methodology has been performed using electrocorticography (ECoG) and implanted grids on the surface of grey matter for pre-surgical planning of drug r...
For more than one century, brain processing was mainly thought in a localisationist framework, in... more For more than one century, brain processing was mainly thought in a localisationist framework, in which one given function was underpinned by a discrete, isolated cortical area, and with a similar cerebral organization across individuals. However, advances in brain mapping techniques in humans have provided new insights into the organizational principles of anatomo-functional architecture. Here, we review recent findings gained from neuroimaging, electrophysiological as well as lesion studies. Based upon these recent data on brain connectome, we challenge the traditional, outdated localisionnist view, and propose an alternative meta-networking theory. This model holds that complex cognitions and behaviors arise from the spatiotemporal integration of distributed but relatively specialized networks underlying conation and cognition (e.g. language, spatial cognition). Dynamic interactions between such circuits result in a perpetual succession of new equilibrium states, opening the door...
Although the occurrence of the supplementary motor area (SMA) syndrome has been extensively repor... more Although the occurrence of the supplementary motor area (SMA) syndrome has been extensively reported following mesial lobe surgery, to our knowledge the time course of disease onset was never accurately documented. We describe a patient without deficit, despite harboring a glioma invading the left SMA. This patient was operated under local anesthesia, to perform intraoperative online sensorimotor and language mapping using electrical stimulations throughout the resection. No deficit was noted at the end of the tumor and SMA removal. The patient was maintained awake to perform an immediate control MRI. Aphasia and right hemiplegia occurred 30 min after the SMA resection. Total recovery was observed within 2 months. This work shows that the SMA syndrome may not occur immediately after SMA resection. We suggest that the transient compensation of the SMA function is likely due to residual activity of an oscillatory loop and/or short-term plasticity (rapid unmasking of parallel networks), with final recovery occurring due to long-term plasticity (neosynaptogenesis).
Intraoperative electrical stimulation, which temporarily inactivates restricted regions during br... more Intraoperative electrical stimulation, which temporarily inactivates restricted regions during brain surgery, can map cognitive functions in humans with spatiotemporal resolution unmatched by other methods. Using this technique, we found that stimulation of the right inferior parietal lobule or the caudal superior temporal gyrus, but not of its rostral portion, determined rightward deviations on line bisection. However, the strongest shifts occurred with subcortical stimulation. Fiber tracking identified the stimulated site as a section of the superior occipitofrontal fasciculus, a poorly known parietal-frontal pathway. These findings suggest that parietal-frontal communication is necessary for the symmetrical processing of the visual scene.
BACKGROUND: The traditional neurosurgical approach to cerebral lesions is based on the classic vi... more BACKGROUND: The traditional neurosurgical approach to cerebral lesions is based on the classic view of a rigid brain organization in fixed “eloquent” areas. However, this method is brought into discussion by the conceptual and methodological advances in neurosciences that provide a more dynamic representation of the anatomo-functional distribution of the human central nervous system (CNS). OBJECTIVE AND METHODS: We review the relevant literature concerning the main features of the modern CNS representation and their implications in neurosurgical practice. RESULTS: The CNS is an integrated, wide, plastic network made up of cortical functional epicenters, “topic organization,” connected by both short-local and large-scale white matter fibers, ie, “hodological organization.” According to this model, called hodotopic, brain function results from parallel streams of information dynamically modulated within an interactive, multimodal, and widely distributed circuit. The application of thi...
BACKGROUND: Awake brain tumor surgery is a unique opportunity for mapping sensorimotor and cognit... more BACKGROUND: Awake brain tumor surgery is a unique opportunity for mapping sensorimotor and cognitive functions, allowing the operator to optimize the resection while preserving the patient's quality of life. During this type of procedure, active participation of the patient is necessary. OBJECTIVE: To assess the efficacy and safety of a method of intermittent general anesthesia with controlled ventilation for performing invasive cerebral mapping. METHODS: We report our prospective and observational single-center study with an asleep-awake-asleep protocol. Aspects of feasibility, airway management, timing of each phase, and occurrence of adverse events were detailed. RESULTS: During a 35-month period, 140 patients underwent resection of a glioma in an eloquent area. During the asleep phases, controlled ventilation with a laryngeal mask was always efficient. Orotracheal intubation was performed for some patients for the second asleep period. The patients remained fully awake for a...
OBJECTIVE AND IMPORTANCE We describe an atypical case of transient Foix-Chavany-Marie syndrome, o... more OBJECTIVE AND IMPORTANCE We describe an atypical case of transient Foix-Chavany-Marie syndrome, or faciopharyngoglossomasticatory diplegia with automatic voluntary dissociation, occurring after surgical resection of a right insulo-opercular glioma. CLINICAL PRESENTATION A 26-year-old right-handed man experienced partial seizures that were poorly controlled by antiepileptic drugs during a 2-year period as a result of a right insulo-opercular low-grade glioma, leading to the proposal of surgical resection. In addition, 1 year before the operation, the patient experienced a severe brain injury that resulted in a coma. A computed tomographic scan revealed left opercular contusion. The patient recovered completely within 6 months. INTERVENTION Intraoperative corticosubcortical electrical functional mapping was performed along the resection, allowing the identification and preservation of the facial and upper limb motor structures. A subtotal removal of the glioma was achieved. The patien...
Object Despite better knowledge of cortical language organization, its subcortical anatomofunctio... more Object Despite better knowledge of cortical language organization, its subcortical anatomofunctional connectivity remains poorly understood. The authors used intraoperative subcortical stimulation in awake patients undergoing operation for a glioma in the left dominant hemisphere to map the language pathways and to determine the contribution of such a method to surgical results. Methods One hundred fifteen patients harboring a World Health Organization Grade II glioma within language areas underwent operation after induction of local anesthesia, using direct electrical stimulation to perform online cortical and subcortical language mapping throughout the resection. Results After detection of cortical language sites, the authors identified 1 or several of the following subcortical language pathways in all patients: 1) arcuate fasciculus, eliciting phonemic paraphasia when stimulated; 2) inferior frontooccipital fasciculus, generating semantic paraphasia when stimulated; 3) subcallosa...
For many decades, interactions between diffuse lower-grade glioma (LGG) and brain connectome were... more For many decades, interactions between diffuse lower-grade glioma (LGG) and brain connectome were neglected. However, the neoplasm progression is intimately linked to its environment, especially the white matter (WM) tracts and their myelin status. First, while the etiopathogenesis of LGG is unclear, this tumor seems to appear during the adolescence, and it is mostly located within anterior and associative cerebral areas. Because these structures correspond to those which were myelinated later in the brain maturation process, WM myelination could play a role in the development of LGG. Second, WM fibers and the myelin characteristics also participate in LGG diffusion, since glioma cells migrate along the subcortical pathways, especially when exhibiting a demyelinated phenotype, which may result in a large invasion of the parenchyma. Third, such a migratory pattern can induce functional (neurological, cognitive and behavioral) disturbances, because myelinated WM tracts represent the m...
The concept of plasticity describes the mechanisms that rearrange cerebral organization following... more The concept of plasticity describes the mechanisms that rearrange cerebral organization following a brain injury. During the last century, plasticity has beenmainly investigated in humans with acute strokes. It was then shown: (i) that the brain is organized into highly specialized functional areas, often designated ‘eloquent ’ areas and (ii) that a lesion within the eloquent area gives rise tomajor irrevocable deficits. However, in sharp contrast with these observations, it was recently found that patients with low-grade gliomas were able to undergo massive cerebral resections without detectable functional consequence. In this paper, we tackle this puzzling observation and address the idea that brain plasticity cannot be fully understood and fruitfully studied without considering the temporal pattern of the injury inflicted to the brain. To achieve this goal, we first review experimental evidence showing that functional recovery is considerably better in the context of slow-growing...
Diffuse low-grade glioma (DLGG) is a chronic tumoral disease that ineluctably grows, migrates alo... more Diffuse low-grade glioma (DLGG) is a chronic tumoral disease that ineluctably grows, migrates along white matter pathways, and progresses to higher grade of malignancy. Rather than a “wait and watch” policy, a therapeutic attitude is currently the gold standard, with early radical safe surgery as the first treatment. Indeed, intraoperative mapping in awake patients, with maximal resection up to functional boundaries, is significantly associated with a longer overall survival (OS), while preserving or even improving quality of life (QoL). However, most of traditional studies have investigated the impact of only one specific therapy (e.g. impact of surgery, or radiotherapy, or chemotherapy) on OS, without a comprehensive view of the whole management strategy on the patient’s cumulative time with preserved QoL versus time to malignant transformation. Here, our goal is to switch towards a more holistic concept, based on the anticipation of a personalized and long-term multistage therapeutic approach, with on-line adaptation of the strategy over years using feedback issued from clinical, radiological and histomolecular monitoring at the individual level. This dynamic and multistage approach challenges the classical strategy by proposing earlier therapy, by repeating treatments, and by reversing the traditional order of therapies (e.g. neoadjuvant chemotherapy if at least subtotal surgical resection is not possible, no early irradiation), to improve both OS and QoL. Neuro-oncologists should tailor their management strategy during the follow-up on the basis of real-time oncological control and functional outcome. Thus, we propose new personalized strategies dealing with the interactions between the natural course of DLGG, reaction neuroplasticity, and onco-functional modulation induced by serial treatments. The ultimate aim is taking measures to delay malignant transformation as long as possible, while giving DLGG patients a real life that includes planning for their long-term future (e.g. such as deciding whether to have a baby). This philosophy supports an individualized, functional, and preventive neurooncology.
IRECT electrical stimulation (DES) has long been used to perform real-time functional mapping of ... more IRECT electrical stimulation (DES) has long been used to perform real-time functional mapping of the brain. More recently, this technique was introduced in the neurosurgery of slow-growing and infiltrative brain tumors to guide the resection with great success. By generating transient perturbations, this method allows the real-time identification of both cortical areas and subcortical networks that are essential for the function. Thus, as much as possible, non-functional tissue can be removed while minimizing the sequelae. However, the understanding of the electrophysiological effects of DES and, in particular its remote propagation, remains an open and key question. DES can be used to probe on-line and in-vivo the spatio-temporal connectivity and the dynamics of functional networks by associating electrophysiological recordings. Such methodology has been performed using electrocorticography (ECoG) and implanted grids on the surface of grey matter for pre-surgical planning of drug r...
For more than one century, brain processing was mainly thought in a localisationist framework, in... more For more than one century, brain processing was mainly thought in a localisationist framework, in which one given function was underpinned by a discrete, isolated cortical area, and with a similar cerebral organization across individuals. However, advances in brain mapping techniques in humans have provided new insights into the organizational principles of anatomo-functional architecture. Here, we review recent findings gained from neuroimaging, electrophysiological as well as lesion studies. Based upon these recent data on brain connectome, we challenge the traditional, outdated localisionnist view, and propose an alternative meta-networking theory. This model holds that complex cognitions and behaviors arise from the spatiotemporal integration of distributed but relatively specialized networks underlying conation and cognition (e.g. language, spatial cognition). Dynamic interactions between such circuits result in a perpetual succession of new equilibrium states, opening the door...
Although the occurrence of the supplementary motor area (SMA) syndrome has been extensively repor... more Although the occurrence of the supplementary motor area (SMA) syndrome has been extensively reported following mesial lobe surgery, to our knowledge the time course of disease onset was never accurately documented. We describe a patient without deficit, despite harboring a glioma invading the left SMA. This patient was operated under local anesthesia, to perform intraoperative online sensorimotor and language mapping using electrical stimulations throughout the resection. No deficit was noted at the end of the tumor and SMA removal. The patient was maintained awake to perform an immediate control MRI. Aphasia and right hemiplegia occurred 30 min after the SMA resection. Total recovery was observed within 2 months. This work shows that the SMA syndrome may not occur immediately after SMA resection. We suggest that the transient compensation of the SMA function is likely due to residual activity of an oscillatory loop and/or short-term plasticity (rapid unmasking of parallel networks), with final recovery occurring due to long-term plasticity (neosynaptogenesis).
Intraoperative electrical stimulation, which temporarily inactivates restricted regions during br... more Intraoperative electrical stimulation, which temporarily inactivates restricted regions during brain surgery, can map cognitive functions in humans with spatiotemporal resolution unmatched by other methods. Using this technique, we found that stimulation of the right inferior parietal lobule or the caudal superior temporal gyrus, but not of its rostral portion, determined rightward deviations on line bisection. However, the strongest shifts occurred with subcortical stimulation. Fiber tracking identified the stimulated site as a section of the superior occipitofrontal fasciculus, a poorly known parietal-frontal pathway. These findings suggest that parietal-frontal communication is necessary for the symmetrical processing of the visual scene.
BACKGROUND: The traditional neurosurgical approach to cerebral lesions is based on the classic vi... more BACKGROUND: The traditional neurosurgical approach to cerebral lesions is based on the classic view of a rigid brain organization in fixed “eloquent” areas. However, this method is brought into discussion by the conceptual and methodological advances in neurosciences that provide a more dynamic representation of the anatomo-functional distribution of the human central nervous system (CNS). OBJECTIVE AND METHODS: We review the relevant literature concerning the main features of the modern CNS representation and their implications in neurosurgical practice. RESULTS: The CNS is an integrated, wide, plastic network made up of cortical functional epicenters, “topic organization,” connected by both short-local and large-scale white matter fibers, ie, “hodological organization.” According to this model, called hodotopic, brain function results from parallel streams of information dynamically modulated within an interactive, multimodal, and widely distributed circuit. The application of thi...
BACKGROUND: Awake brain tumor surgery is a unique opportunity for mapping sensorimotor and cognit... more BACKGROUND: Awake brain tumor surgery is a unique opportunity for mapping sensorimotor and cognitive functions, allowing the operator to optimize the resection while preserving the patient's quality of life. During this type of procedure, active participation of the patient is necessary. OBJECTIVE: To assess the efficacy and safety of a method of intermittent general anesthesia with controlled ventilation for performing invasive cerebral mapping. METHODS: We report our prospective and observational single-center study with an asleep-awake-asleep protocol. Aspects of feasibility, airway management, timing of each phase, and occurrence of adverse events were detailed. RESULTS: During a 35-month period, 140 patients underwent resection of a glioma in an eloquent area. During the asleep phases, controlled ventilation with a laryngeal mask was always efficient. Orotracheal intubation was performed for some patients for the second asleep period. The patients remained fully awake for a...
OBJECTIVE AND IMPORTANCE We describe an atypical case of transient Foix-Chavany-Marie syndrome, o... more OBJECTIVE AND IMPORTANCE We describe an atypical case of transient Foix-Chavany-Marie syndrome, or faciopharyngoglossomasticatory diplegia with automatic voluntary dissociation, occurring after surgical resection of a right insulo-opercular glioma. CLINICAL PRESENTATION A 26-year-old right-handed man experienced partial seizures that were poorly controlled by antiepileptic drugs during a 2-year period as a result of a right insulo-opercular low-grade glioma, leading to the proposal of surgical resection. In addition, 1 year before the operation, the patient experienced a severe brain injury that resulted in a coma. A computed tomographic scan revealed left opercular contusion. The patient recovered completely within 6 months. INTERVENTION Intraoperative corticosubcortical electrical functional mapping was performed along the resection, allowing the identification and preservation of the facial and upper limb motor structures. A subtotal removal of the glioma was achieved. The patien...
Object Despite better knowledge of cortical language organization, its subcortical anatomofunctio... more Object Despite better knowledge of cortical language organization, its subcortical anatomofunctional connectivity remains poorly understood. The authors used intraoperative subcortical stimulation in awake patients undergoing operation for a glioma in the left dominant hemisphere to map the language pathways and to determine the contribution of such a method to surgical results. Methods One hundred fifteen patients harboring a World Health Organization Grade II glioma within language areas underwent operation after induction of local anesthesia, using direct electrical stimulation to perform online cortical and subcortical language mapping throughout the resection. Results After detection of cortical language sites, the authors identified 1 or several of the following subcortical language pathways in all patients: 1) arcuate fasciculus, eliciting phonemic paraphasia when stimulated; 2) inferior frontooccipital fasciculus, generating semantic paraphasia when stimulated; 3) subcallosa...
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Papers by Hugues Duffau