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Biomedical subjects

Hugues Duffau

Publications and source records attributed to Hugues Duffau.

At least 19 recordsLinked to original sources

Beyond one-to-one mappings: Modelling distributed lesion-symptom relationships with multilayer networks.

Lesion-symptom mapping is widely used to identify causal relationships between brain structures and behaviour, and has played a central role in neuropsychologically informed network models of cognition. However, even recent approaches remain constrained by a one-to-one mapping framework, which oversimplifies the complex relationships between network-level damage and cognitive deficits. In addition, the non-orthogonality of cortical and white matter damage makes it difficult to disentangle their distinct contributions. Here, we used graph-based multilayer network analysis to address these limitations and evaluate clinical relevance. Using neuroanatomical and longitudinal neuropsychological data from 252 patients who underwent awake neurosurgery for low-grade glioma, we constructed interactive, three-layer networks for each hemisphere. Layer 1 comprised neuropsychological tasks (NT), layer 2 structural disconnections (SD), and layer 3 cortical damage (CD). Nodes represented tasks, white matter tracts, and cortical parcels, respectively, whereas within-layer edges captured correlations in performance or co-occurring damage patterns. Multilayer community detection identified domain- and hemisphere-specific brain-behaviour motifs linking executive, language, and spatial functions to distinct combinations of cortical and white matter disruption, a pattern confirmed by two spatial embedding approaches. Centrality analyses revealed a continuum of mapping relationships, ranging from one-to-one to one-to-many associations, indicating that tasks such as verbal fluency are better explained by multiple disconnection mechanisms. Additional analyses uncovered many-to-one and many-to-many relationships and highlighted tracts and cortical regions with domain-general relevance. Together, these findings support a neurobiologically grounded, network-oriented account of how structural brain damage gives rise to cognitive deficits, with implications for clinical care.

Humans↗

Beyond motor: clinical manifestations of right hemisphere gliomas - a systematic review.

PURPOSE: Right-hemisphere gliomas have traditionally been regarded as less eloquent than left-sided lesions, influencing surgical decision-making and anesthetic approach. However, these tumors produce diverse non-motor manifestations affecting cognition, behavior, and socio-emotional functioning with important consequences for quality of life. This review aimed to characterize these manifestations and their implications for functional eloquence. METHODS: Following PRISMA guidelines, PubMed, Scopus, and Embase were searched using predefined terms for right-hemisphere gliomas and their manifestations. Eligible studies included patients with supratentorial right-hemisphere gliomas reporting motor and/or non-motor clinical manifestations. Studies were excluded if the clinical presentation was incompletely described or if glioma pathology lacked histopathological confirmation. Extracted data included tumor location, histopathology, clinical manifestations, neuropsychological assessments, and functional outcomes. RESULTS: A total of 372 patients from 88 studies were included. Median age was 42 years (range, 11-87), with slight male predominance (49% vs. 48% female). Preoperative non-motor manifestations were common and heterogeneous, most frequently compromising cognition and executive performance (43%), followed by vision and visuospatial deficits (28.4%) and language deficits (24%). Postoperatively, the most common deficits involved language (46%), followed by vision and visuospatial deficits (40%), and cognition and executive dysfunction (23.1%). Analyses relating extent of resection to postoperative deficits were considered exploratory because reporting of extent of resection and postoperative outcome assessment were incomplete and heterogeneous. CONCLUSIONS: Right-hemisphere gliomas carry a substantial and under-recognized burden of non-motor manifestations that challenge conventional definitions of functional eloquence and support the expansion of functional assessment and surgical planning encompassing right-hemisphere cognitive and behavioral networks.

Humans↗

Involuntary language switching in two bilingual patients during the Wada test and intraoperative electrocortical stimulation.

We present two bilingual patients without language disorders in whom involuntary language switching was induced. The first patient switched from Dutch to English during a left-sided amobarbital (Wada) test. Functional magnetic resonance imaging yielded a predominantly left-sided language distribution similar for both languages. The second patient switched from French to Chinese during intraoperative electrocortical stimulation of the left inferior frontal gyrus. We conclude that the observed language switching in both cases was not likely the result of a selective inhibition of one language, but the result of a temporary disruption of brain areas that are involved in language switching. These data complement the few lesion studies on (involuntary or unintentional) language switching, and add to the functional neuroimaging studies of switching, monitoring, and controlling the language in use.

Adult↗

Contrasting acute and slow-growing lesions: a new door to brain plasticity.

The concept of plasticity describes the mechanisms that rearrange cerebral organization following a brain injury. During the last century, plasticity has been mainly 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 to major 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 injuries than after acute lesions. Both human and animal data are considered. In a second step, we emphasize that slow and acute lesions involve very different patterns of reorganization. In agreement with this idea, we show that the recruitment of remote brain areas in the ipsi- and contralesional hemispheres is much more efficient in slow growing than acute lesions. Finally in a last section, we briefly discuss the main implications of these results.

Acute Disease↗

Brain plasticity: from pathophysiological mechanisms to therapeutic applications.

Cerebral plasticity, which is the dynamic potential of the brain to reorganize itself during ontogeny, learning, or following damage, has been widely studied in the last decade, in vitro, in animals, and also in humans since the development of functional neuroimaging. In the first part of this review, the main hypotheses about the pathophysiological mechanisms underlying plasticity are presented. At a microscopic level, modulations of synaptic efficacy, unmasking of latent connections, phenotypic modifications and neurogenesis have been identified. At a macroscopic level, diaschisis, functional redundancies, sensory substitution and morphological changes have been described. In the second part, the behavioral consequences of such cerebral phenomena in physiology, namely the "natural" plasticity, are analyzed in humans. The review concludes on the therapeutic implications provided by a better understanding of these mechanisms of brain reshaping. Indeed, this plastic potential might be 'guided' in neurological diseases, using rehabilitation, pharmacological drugs, transcranial magnetic stimulation, neurosurgical methods, and even new techniques of brain-computer interface - in order to improve the quality of life of patients with damaged nervous systems.

Animals↗

Preoperative estimation of residual volume for WHO grade II glioma resected with intraoperative functional mapping.

Despite the lack of class I evidence, it is widely agreed that surgery can improve the functional and vital prognosis for WHO grade II gliomas when the resection is at least subtotal radiologically, that is, leaving less than 10 cm(3) of visible residual tumor. Because these tumors frequently invade functional areas, the preoperative estimation of the probable residual volume remains challenging. This article presents a probabilistic map of postoperative residues, with the aim of predicting before the decision for surgical intervention whether the resection could be subtotal. We selected 65 patients who underwent surgery with intraoperative functional mapping between 1999 and 2004 for a WHO grade II glioma located in a sensorimotor and/or language area. For each case, the postoperative image was normalized on a standard atlas, and the residual tumor was segmented. A probabilistic map of residues was then computed. The fusion between the map and a preoperative image allowed a preoperative estimation of the expected extent of resection. The map enhances the regions where grade II glioma cannot be resected. The success rate for the preoperative classification of partial versus subtotal resection is 82%. Although both its reliability and accuracy have to be improved, this probabilistic map gives preoperatively an objective estimation of the expected extent of resection for grade II glioma resected under intraoperative functional mapping. This rationale will assist in decisions regarding surgical resection and may thus contribute to the elaboration of a therapeutic consensus for WHO grade II glioma.

Brain Mapping↗

Superior longitudinal fasciculus subserves vestibular network in humans.

Vestibular function is known to be represented in a large-scale network within the brain. Although much is known about the topography of this cortical network, the subcortical anatomo-functional connectivity has received less attention. We present three patients operated on while conscious for cerebral low-grade gliomas, in which we elicited vestibular symptoms during subcortical stimulation. Anatomo-functional correlations between postoperative imaging and intraoperative findings suggest the involvement of the superior longitudinal fasciculus in the spreading of the vestibular symptoms. We argue that this fasciculus plays a major role in the functional connectivity of the areas involved in the complex multimodal network that controls vestibular function.

Auditory Pathways↗

Assessment of verbal working memory before and after surgery for low-grade glioma.

OBJECT: While scarcely reported in low-grade glioma (LGG), accurate assessment of higher functions is essential to evaluate then preserve the quality of life. We assessed verbal working memory (vWM) in patients with LGG in language areas, before and after surgery, to evaluate the effect of glioma and resection on cognition, respectively. METHODS: About 23 patients harboring a LGG in language areas underwent awake surgery. All patients had a vWM assessment, before and immediately after the resection, in addition to KPS. vWM was also evaluated 3 months after surgery in eight patients (KPS in all cases), who performed postoperative rehabilitation. RESULTS: Preoperatively, 91% of patients had vWM disorders (KPS > or =90 in 22 patients). Immediately after surgery, 96% of patients had vWM worsening (50% of KPS > or =90). At 3 months, among the eight patients examinated, five recovered their preoperative vWM score, and three significantly improved it (KPS > or =90 in 23 patients). CONCLUSION: In LGG, neuropsychological assessment is encouraged in addition to KPS. vWM evaluation before treatment showed that most patients had a cognitive deficit. Moreover, surgery induced a transient vWM worsening, which nevertheless recovers within 3 months. Specific rehabilitation might help to recover and even to improve the preoperative cognitive status.

Adult↗

Partial correlation for functional brain interactivity investigation in functional MRI.

Examination of functional interactions through effective connectivity requires the determination of three distinct levels of information: (1) the regions involved in the process and forming the spatial support of the network, (2) the presence or absence of interactions between each pair of regions, and (3) the directionality of the existing interactions. While many methods exist to select regions (Step 1), very little is available to complete Step 2. The two main methods developed so far, structural equation modeling (SEM) and dynamical causal modeling (DCM), usually require precise prior information to be used, while such information is sometimes lacking. Assuming that Step 1 was successfully completed, we here propose a data-driven method to deal with Step 2 and extract functional interactions from fMRI datasets through partial correlations. Partial correlation is more closely related to effective connectivity than marginal correlation and provides a convenient graphical representation for functional interactions. As an instance of brain interactivity investigation, we consider how simple hand movements are processed by the bihemispheric cortical motor network. In the proposed framework, Bayesian analysis makes it possible to estimate and test the partial statistical dependencies between regions without any prior model on the underlying functional interactions. We demonstrate the interest of this approach on real data.

Cerebral Cortex↗

Radical surgery after chemotherapy: a new therapeutic strategy to envision in grade II glioma.

While surgery is proned in low-grade glioma (LGG), the invasion of functional areas frequently prevents a complete resection. We report the first case of a patient operated on for a left frontal LGG, diagnosed because of seizures, with partial resection due to an invasion of the controlateral hemisphere. Chemotherapy enabled a regression of this controlateral extension. Postchemotherapy surgery performed with intraoperative functional mapping then allowed a complete resection, without sequelae. The patient has a normal socio-professional life, with no seizure. No other treatment was given. There was no recurrence, with a follow-up of 2 years since the second surgery (3.5 years since the first symptom). We propose a new therapeutic strategy in unresectable LGG, with preoperative chemotherapy, to make a radical surgery possible in a second step, while preserving the quality of life.

Adult↗

Extension of paralimbic low grade gliomas: toward an anatomical classification based on white matter invasion patterns.

OBJECT: Low grade gliomas are both proliferative and diffusive tumors, as recently modelized. When proliferation is predominant, the tumor is rather bulky and its main locations are the supplementary motor area and the paralimbic system. Diffusion occurs preferentially along white matter tracts. Recent anatomo-functional studies, performed both in vitro and in vivo, have described the fiber tracts centered around the insula. We thus propose to analyze the extension of paralimbic low grade gliomas in terms of invaded subcortical pathways. METHODS: We retrospectively reviewed the MRIs of patients followed for a WHO grade II glioma at the Salpêtrière Hospital between 1991 and 2003. We selected patients with tumors centered on the insula and extending in temporal and frontal lobes (Type 2b-2c-3 of Yasargil's classification). We then analyzed on FLAIR sequences the extension (tracked on successive examinations before any treatment) along two main fasciculi in that area: the uncinate and arcuate fasciculi. RESULTS: A total of 40 patients fulfilled the inclusion criteria. The uncinate fasiculus was invaded in 28 cases, the arcuate fasciculus in 9 cases, and both fasciculi in 3 cases. Longitudinal follow-up was available in 16 cases, and confirmed the preferential extension along these fasciculi. CONCLUSION: This kinetic analysis of extension of paralimbic low grade gliomas confirms that these tumors spread along distinct subcortical fasciculi. Due to the functional role of these pathways, this classification could be useful to elaborate therapeutic strategy (prognosis index, pre- and intra-operative neuropsychological testing, functional outcome).

Adolescent↗

New concepts in surgery of WHO grade II gliomas: functional brain mapping, connectionism and plasticity--a review.

Despite a recent literature supporting the impact of surgery on the natural history of low-grade glioma (LGG), the indications of resection still remain a matter of debate, especially because of the frequent location of these tumors within eloquent brain areas - thus with a risk to induce a permanent postoperative deficit. Therefore, since the antagonist nature of this surgery is to perform the most extensive glioma removal possible, while preserving the function and the quality of life, new concepts were recently applied to LGG resection in order to optimize the benefit/risk ratio of the surgery.First, due to the development of functional mapping methods, namely perioperative neurofunctional imaging and intrasurgical direct electrical stimulation, the study of cortical functional organization is currently possible for each patient - in addition to an extensive neuropsychological assessment. Such knowledge is essential because of the inter-individual anatomo-functional variability, increased in tumors due to cerebral plasticity phenomena. Thus, brain mapping enables to envision and perform a resection according to individual functional boundaries.Second, since LGG invades not only cortical but also subcortical structures, and shows an infiltrative progression along the white matter tracts, new techniques of anatomical tracking and functional mapping of the subcortical white matter pathways were also used with the goal to study the individual effective connectivity - which needs imperatively to be preserved during the resection.Third, the better understanding of brain plasticity mechanisms, induced both by the slow-growing LGG and by the surgery itself, were equally studied in each patient and applied to the surgical strategy by incorporating individual dynamic potential of reorganization into the operative planning. The integration of these new concepts of individual functional mapping, connectivity and plastic potential to the surgery of LGG has allowed an extent of surgical indications, an optimization of the quality of resection (neuro-oncological benefit), and a minimization of the risk of sequelae (benefit on the quality of life). In addition, such a strategy has also fundamental applications, since it represents a new door to the connectionism and cerebral plasticity.

Brain Mapping↗

Prognostic value of initial magnetic resonance imaging growth rates for World Health Organization grade II gliomas.

A consecutive series of 143 unselected adult patients with histologically proved World Health Organization grade II gliomas was reviewed to assess the prognostic value of growth rates of mean tumor diameters on successive magnetic resonance images before treatment. There is an inverse correlation between growth rates and survival (p < 0.001; median survival at 5.16 years for a growth rate of 8mm/year or more; median survival >15.0 years for a growth rate <8mm/year). Thus, individual magnetic resonance imaging tumor growth rates should be incorporated in the planning of the initial therapeutic strategy of grade II gliomas.

Adolescent↗

[Low grade gliomas and cerebral plasticity: fundamental and clinical implications].

Post-lesional plasticity (PLP) describes the processes that reorganize cerebral connections after an injury. Since Broca's influential contribution and the common endorsement of "localisationist" models of brain physiology, it has been widely admitted that PLP was limited, not to say impossible in the so-called "eloquent areas". However, recent observations associated with the surgical treatments of low grade gliomas have called this dogma into question. Indeed, more and more evidence suggest that large cerebral resections can be compensated so efficiently that no functional deficits can be detected after the surgery. Pre and post surgical investigations based on imaging techniques, as well as intra-surgical investigations involving electrical stimulations, allow to track the nature and the temporal characteristics of these compensations. Compensatory reactions begin before the operation, in response to the tumoral growth. They remain active during and after the surgery. These compensations can involve the perilesional adjacent areas, the distant ipsilateral cerebral structures and the homologous contra-lateral regions. When considered together these results have obvious fundamental and clinical implications. They open new perspectives for understanding cerebral dynamics and the process of brain plasticity.

Aphasia↗

Episodic nocturnal wandering in a patient with epilepsy due to a right temporoinsular low-grade glioma: relief following resection. Case report.

Although controversial, episodic nocturnal wandering (ENW) is thought to be a rare and atypical form of nocturnal epilepsy, originating in the frontal lobe and responsive to antiepileptic drugs (AEDs). The authors report the case of a patient harboring a right temporoinsular low-grade glioma, who presented with a 3-year history of agitated somnambulent episodes resistant to AEDs. Interestingly, the ENW totally resolved after tumor resection and the patient reported no recurrence during a follow-up period of 4.5 years. To the authors' knowledge, this is the first report of ENW due to a glioma; the findings support the theory that ENW may represent an unusual type of lesional epilepsy that is surgically correctable. Moreover, a temporoinsular origin of ENW can now be considered.

Adult↗

Peripheral primitive neuroectodermal tumor of the cauda equina in an elderly patient. Case report.

Primitive neuroectodermal tumors (PNETs) are aggressive neoplasms composed predominantly of undifferentiated cells that show evidence of neural differentiation. Although their classification remains disputed, PNETs are recognized as primary tumors in both the central and peripheral nervous systems. These rare tumors usually occur in children or young adults and are typically metastatic to the spinal cord. The authors report the case of a 70-year-old man with no significant medical history, in whom a peripheral PNET was demonstrated that, based on clinical and imaging findings, manifested as a nonspecific intrathecal tumoral process arising from the cauda equina. Although this lesion is rare in the elderly, the authors' case illustrates the importance of making this diagnosis as early as possible so that a treatment plan may be devised. The use of chemotherapy in association with radiotherapy in relation to the resection of the tumor should be reconsidered.

Aged↗

The insular lobe and brain plasticity: Lessons from tumor surgery.

OBJECTIVES: Despite recent literature supporting the likely role of the insula in many functions, the actual participation of this multimodal lobe in the brain functioning remains unclear, i.e. has the insula an essential or compensable role? PATIENTS AND METHODS: We surgically resected an insular low-grade glioma, using intraoperative electrical stimulation, in 42 patients who experienced seizures, but who presented no or only a slight neurological deficit. Surgery was performed under local anesthesia in patients with a lesion in the dominant hemisphere. The resection was systematically stopped according to cortico-subcortical functional boundaries. RESULTS: Intraoperative electrical mapping induced language disturbances, pain and vertigo, but no other side effects were observed. Post-operatively, the patients experienced a transient hemiparesis in 21 cases, language disorders in 10 cases, an athymhormic syndrome in 7 cases, a Foix-Chavany-Marie syndrome in 3 cases, and micturition disturbances in one case. Despite this immediate post-surgical worsening, all the patients recovered their preoperative neurological status within 3 months, except in three cases due to a deep stroke. CONCLUSION: These results show that the insula, a complex associative multimodal structure poorly studied until now, can be functionally compensated. Such a plastic potential may have important fundamental and clinical implications, in particular in the field of oncological neurosurgery.

Adult↗