[Show abstract][Hide abstract] ABSTRACT: The relevance of emotional perception in interpersonal relationships and social cognition has been well documented. Although brain diseases might impair emotional processing, studies concerning emotional recognition in patients with brain tumours are relatively rare. The aim of this study was to explore emotional recognition in patients with gliomas in three conditions (visual, auditory and crossmodal) and to analyse how tumour-related variables (notably, tumour localisation) and patient-related variables influence emotion recognition. Twenty six patients with gliomas and 26 matched healthy controls were instructed to identify 5 basic emotions and a neutral expression, which were displayed through visual, auditory and crossmodal stimuli. Relative to the controls, recognition was weakly impaired in the patient group under both visual and auditory conditions, but the performances were comparable in the crossmodal condition. Additional analyses using the ‘race model’ suggest differences in multisensory emotional integration abilities across the groups, which were potentially correlated with the executive disorders observed in the patients. These observations support the view of compensatory mechanisms in the case of gliomas that might preserve the quality of life and help maintain the normal social and professional lives often observed in these patients.
Brain and Cognition 12/2014; 92(100):92-100. · 2.82 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Diffuse WHO grade II and III gliomas (DGII/IIIG) are rare tumors, with few specific epidemiological studies. We aimed at describing the geographical distribution of a homogeneous series of histologically confirmed DGII/IIIG, over a four-year period (2006-2009), at a national level. The methodology is based on a multidisciplinary national network already established by the French Brain Tumor DataBase and data collected directly from every neuropathology department. Personal home addresses were collected for confirmed cases. For each region, the incidence of DGII/IIIG was analyzed and standardized on the age and sex distribution of the French population. The number of patients with newly diagnosed, histologically confirmed DGII/IIIG was 4,790. The overall crude rate was 19.4/10(6). To enable international comparisons, standardized rates were calculated as follows: 19.8/10(6), 18.8/10(6) and 16.0/10(6) (reference population, Europe, US and world, respectively). The geographical distribution by region showed significant differences, with higher incidence rates in Northeast and central parts of France. This work is the first studying the geographical distribution of a pure series of DGII/IIIG at a national level. It demonstrates significant heterogeneity in the distribution, and raises the question of the role of environmental and/or genetic risk(s) factor(s) for DGII/IIIG.
Journal of Neuro-Oncology 08/2014; · 3.12 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Circulating proteins released by tumor cells have recently been investigated as potential single surrogate biomarkers for glioblastoma multiforme (GBM). The aim of the current hypothesis-generating study was to evaluate the diagnostic and prognostic role of preoperative insulin-like growth factor-binding protein 2 (IGFBP-2), chitinase-3-like protein 1 (YKL-40), and glial fibrillary acidic protein (GFAP) plasma levels in patients with GBM, both as single markers and as a combined profile.
[Show abstract][Hide abstract] ABSTRACT: Brain gliomas are highly epileptogenic. Excitatory glutamatergic mechanisms are involved in the generation of epileptic activities in the neocortex surrounding gliomas. However, chloride homeostasis is known to be perturbed in glioma cells. Thus, the contribution of γ-aminobutyric acidergic (GABAergic) mechanisms that depend on intracellular chloride merits closer study. We studied the occurrence, networks, cells, and signaling basis of epileptic activities in neocortical slices from the peritumoral surgical margin resected around human brain gliomas. Postoperative glioma tissue from 69% of patients spontaneously generated interictal-like discharges, synchronized, with a high-frequency oscillation signature, in superficial layers of neocortex around areas of glioma infiltration. Interictal-like events depended both on glutamatergic AMPA receptor-mediated transmission and on depolarizing GABAergic signaling. GABA released by interneurons depolarized 65% of pyramidal cells, in which chloride homeostasis was perturbed because of changes in expression of neuronal chloride cotransporters: KCC2 (K-Cl cotransporter 2) was reduced by 42% and expression of NKCC1 (Na-K-2Cl cotransporter 1) increased by 144%. Ictal-like activities were initiated by convulsant stimuli exclusively in these epileptogenic areas. This study shows that epileptic activities are sustained by excitatory effects of GABA in human peritumoral neocortex, as reported in temporal lobe epilepsies, suggesting that both glutamate and GABA signaling and cellular chloride regulation processes, all also involved in oncogenesis as already shown, induce an imbalance between synaptic excitation and inhibition underlying epileptic discharges in glioma patients. Thus, the control of chloride in neurons and glioma cells may provide a therapeutic target for patients with epileptogenic gliomas.
Science translational medicine 07/2014; 6(244):244ra89. · 10.76 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We explored whether spontaneous imaging tumor growth (estimated by the velocity of diametric expansion) and isocitrate dehydrogenase 1 (IDH1) mutation (estimated by IDH1 immunoexpression) were independent predictors of long-term outcomes of diffuse low-grade gliomas in adults.
[Show abstract][Hide abstract] ABSTRACT: The incidence of glioblastoma (GBM) has increased in patients aged 70 years or older, and will continue to grow. Elderly GBM patients have been excluded from most clinical trials; furthermore, optimal care management as well as benefit/risk ratio of GBM treatments are still being debated. This study describes oncological patterns of care, prognostic factors, and survival for patients ≥70 years in France. We identified patients over 70 with newly diagnosed and histologically confirmed GBM on data previously published by the French Brain Tumor DataBase. We included 265 patients. Neurological deficits and mental status disorders were the most frequent symptoms. The surgery consisted of resection (RS n = 95) or biopsy (B n = 170); 98 patients did not have subsequent oncological treatment. After surgery, first-line treatment consisted of radiotherapy (RT n = 76), chemotherapy (CT n = 52), and concomitant radiochemotherapy (CRC n = 39). The median age at diagnosis was 76, 74, and 73 years, respectively, for the untreated, B + RT and/or CT, RS ± RT and/or CT groups. Median survival (in days, 95 % CI) with these main strategies, when analyzed according to surgical groups, was: B-CT n = 41, 199[155-280]; B-CRC n = 21, 318[166-480]; B-RT n = 37, 149[130-214]; RS-CT n = 11, 245[211-na]; RS-CRC n = 18, 372[349-593]; RS-RT n = 39, 269[218-343]. This population study for elderly GBM patients is one of the most important in Europe, and could be considered as a historical cohort to compare future treatments. Moreover, we can hypothesize that elderly patients (versus patients <70 years) are undertreated. Karnofsky performance status seems to be the most relevant clinical predictive factor, and RS and CRC have a positive impact on survival for elderly GBM patients in the general population, at least when feasible.
[Show abstract][Hide abstract] ABSTRACT: Diffuse low-grade gliomas are highly epileptogenic brain tumours. We aimed to explore the natural course of epileptic seizures, their predictors and the prognostic significance of their occurrence in adult patients harbouring a diffuse low-grade glioma. An observational retrospective multicentre study examined 1509 patients with diffuse low-grade gliomas to identify mutual interactions between tumour characteristics, tumour course and epileptic seizures. At diagnosis, 89.9% of patients had epileptic seizures. Male gender (P = 0.003) and tumour location within functional areas (P = 0.001) were independent predictors of a history of epileptic seizures at diagnosis. Tumour volume, growth velocity, cortical location, histopathological subtype or molecular markers did not significantly affect epileptic seizure occurrence probability. Prolonged history of epileptic seizures (P < 0.001), insular location (P = 0.003) and tumour location close to functional areas (P = 0.038) were independent predictors of uncontrolled epileptic seizures at diagnosis. Occurrence of epileptic seizures (P < 0.001), parietal (P = 0.029) and insular (P = 0.002) locations were independent predictors of uncontrolled epileptic seizures after oncological treatment. Patient age (P < 0.001), subtotal (P = 0.007) and total (P < 0.001) resections were independent predictors of total epileptic seizure control after oncological treatment. History of epileptic seizures at diagnosis and total surgical resection were independently associated with increased malignant progression-free (P < 0.001 and P < 0.001) and overall (P < 0.001 and P = 0.016) survivals. Epileptic seizures are independently associated with diffuse low-grade glioma prognosis. Patients diagnosed with epileptic seizures and those with complete and early surgical resections have better oncological outcomes. Early and maximal surgical resection is thus required for diffuse low-grade gliomas, both for oncological and epileptological purposes.
[Show abstract][Hide abstract] ABSTRACT: Background
Diffuse low-grade gliomas (LGGs) form a heterogeneous subgroup of gliomas in adults. Chromosome (chr) arms 1p/19q codeletion and IDH mutation have been shown to be closely associated with oligodendroglial phenotype and better prognosis. We sought to identify relevant biomarkers in non 1p/19q codeleted LGGs.Methods
We characterized a retrospective series of 126 LGGs using genomic arrays, microsatellite analysis, IDH sequencing, MGMT promoter methylation assay, and p53 expression analysis.ResultsOur study confirms that 1p/19q codeletion, mutually exclusive with p53 overexpression, was associated with: (i) better prognosis, (ii) oligodendroglial phenotype, (iii) MGMT promoter methylation, and (iv) IDH mutation. Interestingly, 1p/19q codeleted tumors occur in older patients at diagnosis. Our study shows that non 1p/19q codeleted LGGs can be divided in 5 main genomic subgroups: (i) 11p loss, (ii) 19q loss (iii) 7 gain, (iv) 19 gain, and (v) unclassified. In non 1p/19q codeleted LGGs, we demonstrated that (i) 11p loss is associated with astrocytoma phenotype and has an independent negative prognostic value, and (ii) 19q loss diminished the favorable prognostic value of IDH mutation. Our findings were validated in an independent cohort of 98 LGGs.Conclusion
Novel genomic entities and biomarkers have been identified in non 1p/19q codeleted LGGs. Our findings may help to stratify non 1p/19q codeleted LGGs, facilitating future individualization of treatment. Further prospective studies are warranted to support our findings.
[Show abstract][Hide abstract] ABSTRACT: Gliomas are the most frequent primary brain tumors and most glioma patients have seizures. The origin and mechanisms of human glioma-related epilepsy are multifactorial and an intermix of oncologic and neuronal processes. In this brief review, we show that the infiltrated peritumoral neocortex appears to be the key structure for glioma-related epileptic activity, which depends on the interactions between the tumor per se and the surrounding brain. We shed light on the underlying mechanisms from two different "tumorocentric" and "epileptocentric" approaches, with a special emphasis on the glioma-related glutamatergic and γ-aminobutyric acid (GABA)ergic changes leading to epileptogenicity. Because gliomas use the neurotransmitter glutamate as a "tumor growth factor" to enhance glioma cell proliferation and invasion with neurotoxic, proinvasive, and proliferative effects, glutamate homeostasis is impaired, with elevated extracellular glutamate concentrations. Such excitatory effects contribute to the generation of epileptic activity in the peritumoral neocortex. GABAergic signaling is also involved both in tumor growth and in paradoxical excitatory effects mediated by alterations in neuronal and tumor cell Cl(-) homeostasis related to cotransporter changes. Local excitability may also be affected by an increase in extracellular K(+) concentration, the alkalization of peritumoral neocortex, and alterations of gap-junction functioning. Finally, the tumor itself may mechanically affect locally neuronal behavior, connections, and networks. Better understanding of glioma-related oncologic and epileptologic processes are crucial for development of combined therapeutic strategies, but so far, the surgical management of gliomas should comprise a maximally safe surgical resection encompassing peritumoral neocortex.
[Show abstract][Hide abstract] ABSTRACT: It is commonly believed that, before being diagnosed after onset of symptoms, diffuse low-grade glioma evolve silently for a long time. The present study aimed to estimate for the first time the exact duration of this silent phase, during which the glioma is radiologically visible but undiscovered.
We retrospectively reviewed our French national database of diffuse low-grade glioma, searching for patients with an MRI-based assessment of their velocity of diameter growth at diagnosis and before any treatment (at least three MRIs over more than 6 months). For each patient, the duration of the silent phase was estimated by the formula: duration = initial diameter / initial velocity of growth.
A total of 148 patients were included in the study. The mean lead-time duration (i.e., duration of the silent phase) was 14.0 ± 7.8 years (median, 11.6 ; range, 1.6-39.4). The lead-time is statistically not correlated to the tumor volume. It is markedly decreasing with the velocity of diameter expansion.
Diffuse low-grade glioma are radiologically detectable but clinically silent for more than a decade. Such a long period of silent evolution could explain our current failure to cure these tumors. It can also be viewed as a window of opportunity to detect these tumors earlier, suggesting the need to set up a screening program.
[Show abstract][Hide abstract] ABSTRACT: We report the longitudinal case study of a right-handed patient harboring two frontal tumors that benefited from bilateral simultaneous surgery. The tumors were WHO Grade II gliomas located in the left inferior frontal area (including the cingulate gyrus) and the right anterior superior frontal gyrus. The double tumor resection was guided by direct electrical stimulation of brain areas while the patient was awake. Neuropsychological assessments were administered before and after the surgery to analyse how the brain functions in the presence of two frontal gliomas that affect both hemispheres and reacts to a bilateral resection, which can brutally compromise the neuronal connectivity, progressively established during the infiltrating process. We showed that both the tumor infiltration and their bilateral resection did not lead to a "frontal syndrome" or a "dysexecutive syndrome" predicted by the localization models. However, a subtle fragility was observed in fine-grain language, memory and emotional skills. This case study reveals the significance of brain plasticity in the reorganization of cognitive networks, even in cases of bilateral tumors. It also confirms the clinical relevance of hodotopical brain models, which considers the brain to be organized in parallel-distributed networks around cortical centers and epicenters.
[Show abstract][Hide abstract] ABSTRACT: Object The spontaneous prognostic factors and optimal therapeutic strategy for WHO Grade II gliomas (GIIGs) have yet to be unanimously defined. Specifically, the role of resection is still debated, most notably because the actual amount of resection has seldom been assessed. Methods Cases of GIIGs treated before December 2007 were extracted from a multicenter database retrospectively collected since January 1985 and prospectively collected since 1996. Inclusion criteria were a patient age ≥ 18 years at diagnosis, histological diagnosis of WHO GIIG, and MRI evaluation of tumor volume at diagnosis and after initial surgery. One thousand ninety-seven lesions were included in the analysis. The mean follow-up was 7.4 years since radiological diagnosis. Factors significant in a univariate analysis (with a p value ≤ 0.1) were included in the multivariate Cox proportional hazard regression model analysis. Results At the time of radiological diagnosis, independent spontaneous factors of a poor prognosis were an age ≥ 55 years, an impaired functional status, a tumor location in a nonfrontal area, and, most of all, a larger tumor size. When the study starting point was set at the time of first treatment, independent favorable prognostic factors were limited to a smaller tumor size, an epileptic symptomatology, and a greater extent of resection. Conclusions This large series with its volumetric assessment refines the prognostic value of previously stressed clinical and radiological parameters and highlights the importance of tumor size and location. The results support additional arguments in favor of the predominant role of resection, in accordance with recently reported experiences.
Journal of Neurosurgery 03/2013; · 3.15 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: IntroductionFacial and vocal emotions contribute to sustain efficient social relationships. Brain disease may impair their identification. In the case of slow-growth tumors (Low Grade Gliomas [LGG]) or sudden stroke (cerebrovascular accidents [CVA]), the lesions induce contrasted plasticity and reorganisation processes.Methods
We compared the facial, vocal and intermodal identification of six emotions (happiness, fear, angriness, sadness, disgust and neutral) of three groups: patients with LGG before and after tumor resection, patients with CVA and control subjects.ResultsIn LGG patients, the results revealed less efficient performances after tumor resection and in CVA patients weak performances regarding negative emotions. The intermodal condition (simultaneous visual and vocal association) improved performances in all groups and enabled equivalent performance in CVA subjects compared with control subjects.Conclusion
The intergroup differences may be related to variable brain plasticity as a function of type and rapidity of brain injury. Intermodal processing appears to be a compensatory condition.
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND AND IMPORTANCE: Direct puncture may offer an alternative access for embolization of intracranial aneurysms in patients presenting with tortuous vessels. Nevertheless, major complications such as compressive hematoma and arterial dissection can occur with this technique. CLINICAL PRESENTATION: A tight common carotid artery (CCA) dissection was seen secondary to direct puncture in a 72-year-old patient who presented with a ruptured anterior communicating artery (ACom) aneurysm. After regular coiling of the aneurysm and using a femoral approach, an Angio-Seal™ device (St Jude Medical, Saint Paul, MN, USA) was placed and a carotid wallstent (Stryker Neurovascular, Fremont, CA, USA) successfully deployed at the dissected CCA, which was followed by good clinical and angiographic outcomes. CONCLUSION: A combined rescue technique combining Angio-Seal insertion and stent deployment was safe and effective for managing iatrogenic carotid artery dissection.
Journal of Neuroradiology 02/2013; · 1.24 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background
Supratentorial diffuse low-grade gliomas present a slow macroscopic tumor growth that can be quantified through the measurement of their velocity of diametric expansion. We assessed whether spontaneous velocity of diametric expansion can predict long-term outcomes as a categorical variable and as a continuous predictor.MethodsA total of 407 adult patients with newly diagnosed supratentorial diffuse low-grade gliomas in adults were studied.ResultsThe mean spontaneous velocity of diametric expansion before first-line treatment was 5.8 ± 6.3 mm/year. During the follow-up (mean, 86.5 ± 59.4 months), 209 patients presented a malignant transformation, and 87 died. The malignant progression-free survival and the overall survival were significantly longer in cases of slow velocity of diametric expansion (median, 103 and 249 months, respectively) than in cases of fast velocity of diametric expansion (median, 35 and 91 months, respectively; P < .001). In multivariate analyses, spontaneous velocity of diametric expansion as a categorical variable (<4, ≥4 and <8, ≥8 and <12, ≥12 mm/year) was an independent prognostic factor for malignant progression-free survival (P < .001; hazard ratio, 3.87; 95% confidence interval [CI], 2.67-5.52) and for overall survival (P < .001; hazard ratio, 4.62; 95% CI, 2.58-7.97). Velocity of diametric expansion was also an independent prognostic factor for overall survival as a continuous predictor, showing a linear relationship between overall survival and spontaneous velocity of diametric expansion (hazard ratio, 1.09 per one unit increase; 95% CI, 1.06-1.12; P < .001).Conclusions
Independent of the molecular status, the spontaneous velocity of diametric expansion allows the identification of rapidly growing diffuse low-grade gliomas (at higher risk of worsened evolution) during the pretherapeutic period and without delaying treatment.
[Show abstract][Hide abstract] ABSTRACT: PURPOSE: The aim of this study was to compare various acquisition and processing protocols for noninvasive glioma grading using either static or dynamic F-FDopa PET. METHODS: Dynamic studies were performed in 33 patients. Based on histopathological analysis, 18 patients had a high-grade (HG) tumor and 15 patients had a low-grade (LG) tumor. For static imaging, SUVmean and SUVmax were calculated for different acquisition time ranges after injection. For dynamic imaging, the transport rate constant k1 was calculated according to a compartmental kinetic analysis using an image-derived input function. RESULTS: With the use of a 5-minute static imaging protocol starting at 38 minutes after injection, newly diagnosed HG tumors could be distinguished from LG tumors with a sensitivity of 70% and a specificity of 90% with a threshold of SUVmean of 2.5. In recurrent tumors, a sensitivity of 100% and a specificity of 80% for identifying HG tumors were obtained with a threshold set to 1.8. Dynamic imaging only slightly, but nonsignificantly, improved differential diagnosis. CONCLUSIONS: Static and dynamic imaging without blood sampling can discriminate between LG and HG for both newly diagnosed and recurrent gliomas. In dynamic imaging, excellent discrimination was obtained by considering the transport rate constant k1 of tumors. In static imaging, the best discrimination based on SUV was obtained for SUVmean calculated from a 5-minute acquisition started at 38 minutes after injection.
Clinical nuclear medicine 02/2013; 38(2):81-87. · 3.92 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The division of human learning systems into reward and punishment opponent modules is still a debated issue. While the implication of ventral prefrontostriatal circuits in reward-based learning is well established, the neural underpinnings of punishment-based learning remain unclear. To elucidate the causal implication of brain regions that were related to punishment learning in a previous functional neuroimaging study, we tested the effects of brain damage on behavioral performance, using the same task contrasting monetary gains and losses. Cortical and subcortical candidate regions, the anterior insula and dorsal striatum, were assessed in patients presenting brain tumor and Huntington disease, respectively. Both groups exhibited selective impairment of punishment-based learning. Computational modeling suggested complementary roles for these structures: the anterior insula might be involved in learning the negative value of loss-predicting cues, whereas the dorsal striatum might be involved in choosing between those cues so as to avoid the worst.
[Show abstract][Hide abstract] ABSTRACT: Supratentorial hemispheric diffuse low-grade gliomas (LGGs), i.e., World Health Organization grade II gliomas, are a heterogeneous group of tumors. During their natural course, LGGs tend to progress to a higher grade of malignancy, leading to neurological disability and ultimately to death. In this review, we will show, that during their low-grade period, these tumors exhibit systematically a spontaneous and continuous radiological growth, whatever their histological subtypes. The radiological tumor growth is easily quantified by measuring the evolution of the equivalent tumor diameter (calculated from the tumor volume), obtaining the velocity of diametric expansion (VDE). The spontaneous VDE of LGGs varies markedly with an average VDE of about 4 mm/year. It depends on intrinsic factors (1p19q codeletion status, P53 overexpression status) and can be modified by extrinsic factors (pregnancy). The spontaneous VDE carries a strong prognostic significance regarding progression-free and overall survivals. As a consequence, VDE should be integrated along with the other "static" parameters (multimodal imaging, histological and molecular analyses) in the initial investigations. In addition, the assessment of VDE obtained before, during, and after a particular oncological treatment helps in analyzing their effects on LGGs on an individual basis, helping to guide the decision making.