Search

To study changes of thalamo-cortical and cortico-cortical connectivity during wakefulness, non-Rapid Eye Movement (non-REM) sleep, including N2 and N3 stages, and REM sleep, using stereoelectroencephalography (SEEG) recording in humans.We studied SEEG recordings of ten patients during wakefulness, non-REM sleep and REM sleep, in seven brain regions of interest including the thalamus. We calculated directed and undirected functional connectivity using a measure of non-linear correlation coefficient hThe thalamus was more connected to other brain regions during N2 stage and REM sleep than during N3 stage during which cortex was more connected than the thalamus. We found two significant directed links: the first from the prefrontal region to the lateral parietal region in the delta band during N3 sleep and the second from the thalamus to the insula during REM sleep.These results showed that cortico-cortical connectivity is more prominent in N3 stage than in N2 and REM sleep. During REM sleep we found significant thalamo-insular connectivity, with a driving role of the thalamus.We found a pattern of cortical connectivity during N3 sleep concordant with antero-posterior traveling slow waves. The thalamus seemed particularly involved as a hub of connectivity during REM sleep.

Nodular heterotopias (NHs) are malformations of cortical development associated with drug-resistant focal epilepsy with frequent poor surgical outcome. The epileptogenic network is complex and can involve the nodule, the overlying cortex, or both. Single-pulse electrical stimulation (SPES) during stereo-electroencephalography (SEEG) allows the investigation of functional connectivity between the stimulated and responsive cortices by eliciting cortico-cortical evoked potentials (CCEPs). We used SPES to analyze the NH connectome and its relation to the epileptogenic network organization.We retrospectively studied 12 patients with NH who underwent 1 Hz or 0.2 Hz SPES of NH during SEEG. Outbound connectivity (regions where CCEPs were elicited by NH stimulation) and inbound connectivity (regions where stimulation elicited CCEPs in the NH) were searched. SEEG channels were then classified as "heterotopic" (located within the NH), "connected" (located in normotopic cortex and showing connectivity with the NH), and "unconnected." We used the epileptogenicity index (EI) to quantify implication of channels in the seizure-onset zone and to classify seizures as heterotopic, normotopic, and normo-heterotopic.One hundred thirty-five outbound and 72 inbound connections were found. Three patients showed connectivity between hippocampus and NH, and seven patients showed strong internodular connectivity. A total of 39 seizures were analyzed: 23 normo-heterotopic, 12 normotopic, and 4 heterotopic. Logistic regression found that "connected" channels were significantly (p = 8.4e-05) more likely to be epileptogenic than "unconnected" channels (odds ratio 4.71, 95% confidence interval (CI) [2.17, 10.21]) and heterotopic channels were also significantly (p = .024) more epileptogenic than "unconnected" channels (odds ratio 3.29, 95% CI [1.17, 9.23]).SPES reveals widespread connectivity between NH and normotopic regions. Those connected regions show higher epileptogenicity. SPES might be useful to assess NH epileptogenic network.

International audience; Objectives: To assess hippocampal function during stereoelectroencephalography (SEEG) investigations through the study of the medial temporal lobe event-related potential (ERP) MTL-P300. Methods: We recorded the MTL-P300 during a visual oddball task, using hippocampal electrodes implanted for SEEG in 71 patients, in a preoperative epilepsy investigation. The presence of an MTL-P300 and its amplitude were correlated with hippocampal involvement during seizures and memory function. Results: Analysis using ROC curves revealed that an MTL-P300 amplitude below-46 µV, has a specificity of 93.3% in detecting the epileptogenic zone, and absence of the MTL-P300 in the left hippocampus of patients with typical language organization was associated with marked alteration of verbal memory scores. There was a significant correlation between performance in non-verbal memory tests and the amplitude of the MTL-P300 in the right hippocampus of patients with left hemispheric seizures (immediate visual recall: r=0.67, p=0.005; delayed visual recall: r=0.56, p=0.025). Using a linear regression, we confirmed that the absence of the MTL-P300 in the left hippocampus, the involvement of the left hippocampus during seizures, and the duration of epilepsy were predictors of verbal memory deficits. Conclusion: Analysis of the MTL-P300 during SEEG recording provides relevant information for the analysis of hippocampal functionality and can help to localize the epileptogenic zone.

This study was undertaken to characterize clinical expression and intracerebral electroencephalographic (EEG) correlates of emotional expression during prefrontal epileptic seizures.We performed a descriptive analysis of seizure semiology in patients explored with stereo-EEG (SEEG) for pharmacoresistant prefrontal epilepsy, using a semiquantitative score for seizure-related emotional behavior. Two independent observers scored occurrence and intensity of objective emotional features (face/body movements/vocalization/overall appearance), testing interobserver reliability. Intracerebral electrophysiological changes were documented. Cluster analysis and principal component analysis (PCA) compared behavioral signs with neural SEEG correlates. For each patient, the clinical and anatomoelectrophysiological scores were established, based on a prototypical emotional seizure.Forty-two patients (469 seizures) were included. Interobserver correlation for emotional signs was satisfactory (kappa = 0.6-0.8). Prevalence of any subjective and/or objective ictal emotional phenomena was 79% (33/42); objective emotional signs occurred in 27 of 42 subjects (64%). Negatively valenced emotional semiology (ictal feeling of fear, defensive and/or aggressive behaviors) was much more prevalent than positively valenced, prosocial behaviors. Cluster analysis and PCA identified 4 groups with different occurrence of emotional signs and cerebral correlates. Two main clusters of negatively valenced behavior were identified: "active threat response," associated with seizure organizations involving posterior orbitofrontal cortex, anterior cingulate, and dorsolateral and/or ventrolateral prefrontal cortex; and "passive fear," associated with amygdala, other mesial temporal structures, and posterior orbitofrontal cortex.Emotional behaviors, especially fear/threat response, are common in prefrontal seizures, reflecting the role of the prefrontal cortex in emotional control. Different cortical seizure localizations were associated with "passive fear" and "active threat response" seizure behaviors at the group level. ANN NEUROL 2022;92:1052-1065.

The virtual epileptic patient (VEP) is a large-scale brain modeling method based on virtual brain technology, using stereoelectroencephalography (SEEG), anatomical data (magnetic resonance imaging [MRI] and connectivity), and a computational neuronal model to provide computer simulations of a patient's seizures. VEP has potential interest in the presurgical evaluation of drug-resistant epilepsy by identifying regions most likely to generate seizures. We aimed to assess the performance of the VEP approach in estimating the epileptogenic zone and in predicting surgical outcome.VEP modeling was retrospectively applied in a cohort of 53 patients with pharmacoresistant epilepsy and available SEEG, T1-weighted MRI, and diffusion-weighted MRI. Precision recall was used to compare the regions identified as epileptogenic by VEP (EZVEP showed a precision of 64% and a recall of 44% for EZVEP is the first computational model that estimates the extent and organization of the epileptogenic zone network. It is characterized by good precision in detecting epileptogenic regions as defined by a combination of visual analysis and EI. The potential impact of VEP on improving surgical prognosis remains to be exploited. Analysis of factors limiting the performance of the actual model is crucial for its further development.

Objective Non-rapid eye movement (NREM) sleep is supposed to play a key role in long-term memory consolidation transferring information from hippocampus to neocortex. However, sleep also activates epileptic activities in medial temporal regions. This study investigated whether interictal hippocampal spikes during sleep would impair long-term memory consolidation. Method We prospectively measured visual and verbal memory performance in 20 patients with epilepsy investigated with stereoelectroencephalography (SEEG) at immediate, 30-minute, and 1-week delays, and studied the correlations between interictal hippocampal spike frequency during waking and the first cycle of NREM sleep and memory performance, taking into account the number of seizures occurring during the consolidation period and other possible confounding factors, such as age and epilepsy duration. Results Retention of verbal memory over 1 week was negatively correlated with hippocampal spike frequency during sleep, whereas no significant correlation was found with hippocampal interictal spikes during waking. No significant result was found for visual memory. Regression tree analysis showed that the number of seizures was the first factor that impaired the verbal memory retention between 30 minutes and 1 week. When the number of seizures was below 5, spike frequency during sleep higher than 13 minutes was associated with impaired memory retention over 1 week. Interpretation Our results show that activation of interictal spikes in the hippocampus during sleep and seizures specifically impair long-term memory consolidation. We hypothesize that hippocampal interictal spikes during sleep interrupt hippocampal-neocortical transfer of information. ANN NEUROL 2020;87:976-987.

International audience; ObjectiveStereo-electroencephalography (SEEG)-guided radiofrequency thermocoagulation (RF-TC) aims at modifying epileptogenic networks to reduce seizure frequency. High-frequency oscillations (HFOs), spikes, and cross-rate are quantifiable epileptogenic biomarkers. In this study, we sought to evaluate, using SEEG signals recorded before and after thermocoagulation, whether a variation in these markers is related to the therapeutic effect of this procedure and to the outcome of surgery.MethodsInterictal segments of SEEG signals were analyzed in 38 patients during presurgical evaluation. We used an automatized method to quantify the rate of spikes, rate of HFOs, and cross-rate (a measure combining spikes and HFOs) before and after thermocoagulation. We analyzed the differences both at an individual level with a surrogate approach and at a group level with analysis of variance. We then evaluated the correlation between these variations and the clinical response to RF-TC and to subsequent resective surgery.ResultsAfter thermocoagulation, 19 patients showed a clinical improvement. At the individual level, clinically improved patients more frequently had a reduction in spikes and cross-rate in the epileptogenic zone than patients without clinical improvement (p = .002, p = .02). At a group level, there was a greater decrease of HFOs in epileptogenic and thermocoagulated zones in patients with clinical improvement (p < .05) compared to those with no clinical benefit. Eventually, a significant decrease of all the markers after RF-TC was found in patients with a favorable outcome of resective surgery (spikes, p = .026; HFOs, p = .03; cross-rate, p = .03).SignificanceQuantified changes in the rate of spikes, rate of HFOs, and cross-rate can be observed after thermocoagulation, and the reduction of these markers correlates with a favorable clinical outcome after RF-TC and with successful resective surgery. This may suggest that interictal biomarker modifications after RF-TC can be clinically used to predict the effectiveness of the thermocoagulation procedure and the outcome of resective surgery.

Objective Amygdala enlargement is increasingly described in association with temporal lobe epilepsies. Its significance, however, remains uncertain both in terms of etiology and its link with psychiatric disorders and of its involvement in the epileptogenic zone. We assessed the epileptogenic networks underlying drug-resistant epilepsy with amygdala enlargement and investigated correlations between clinical features, epileptogenicity and morphovolumetric amygdala characteristics. Methods We identified 12 consecutive patients suffering from drug-resistant epilepsy with visually suspected amygdala enlargement and available stereoelectroencephalographic recording. The epileptogenic zone was defined using the Connectivity Epileptogenicity Index. Morphovolumetric measurements were performed using automatic segmentation and co-registration on the 7TAMIbrain Amygdala atlas. Results The epileptogenic zone involved the enlarged amygdala in all but three cases and corresponded to distributed, temporal-insular, temporal-insular-prefrontal or prefrontal-temporal networks in ten cases, while only two were temporo-mesial networks. Morphovolumetrically, amygdala enlargement was bilateral in 75% of patients. Most patients presented psychiatric comorbidities (anxiety, depression, posttraumatic stress disorder). The level of depression defined by screening questionnaire was positively correlated with the extent of amygdala enlargement. Conclusions Drug-resistant epilepsy with amygdala enlargement is heterogeneous; most cases implied “temporal plus” networks. Significance The enlarged amygdala could reflect an interaction of stress-mediated limbic network alterations and mechanisms of epileptogenesis.

Objective Postictal generalized suppression (PGES) may be associated with SUDEP risk. We aimed to study metabolic changes on 18Fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) in patients with focal to bilateral (generalized) seizures (GTCS) and PGES on stereoelectroencephalography (SEEG). Methods We analyzed interictal brain metabolism in a group of 19 patients with widespread postictal suppression (PGES+) associated with SEEG-recorded GTCS. This group was compared to 25 patients without widespread suppression (PGES−) as defined by SEEG, matched for epilepsy localization and lateralization. Frequency of GTCS was observed to be higher in the PGES+ group (high risk group for SUDEP). Analysis of metabolic data was performed by statistical parametric mapping (SPM) on the whole-brain, and principal component analysis (PCA) on AAL (automated anatomical labeling) atlas. Results Statistical parametric mapping showed right temporal pole hypometabolism in the PGES+ group (T-score = 3.90; p Significance Interictal metabolic changes within a predominantly right-sided network involving temporal lobe and connected cortical and subcortical structures were seen in patients with frequent GTCS presenting widespread postictal suppression.

International audience; Multicentre studies are of utmost importance to conrm hypotheses. The lack of established standards and the ensuing complexity of their datamanagement often hamper their implementation. The Brain Imaging Data Structure (BIDS) is an initiative for organizing and describing neuroimagingand electrophysiological data. Building on BIDS, we have developed two software programs: BIDS Manager and BIDS Uploader. The former has beendesigned to collect, organise and manage the data and the latter has been conceived to handle their transfer and anonymisation from the partner centres. These two programs aim at facilitating the implementation of multicentre study by providing a standardised framework.

Objectives Parietal lobe seizures (PLS) are characterized by multiple clinical manifestations including motor signs. The mechanisms underlying the occurrence of motor signs are poorly understood. The main objective of this work was to estimate the functional coupling of brain regions associated with this clinical presentation. Methods We retrospectively selected patients affected by drug-resistant epilepsy who underwent Stereoelectroencephalography (SEEG) for pre-surgical evaluation and in whom the seizure onset zone (SOZ) was located in the parietal cortex. The SOZ was defined visually and quantitatively by the epileptogenicity index (EI) method. Two groups of seizures were defined according to the presence (“motor seizures”) or the absence (“non-motor seizures”) of motor signs. Functional connectivity (FC) estimation was based on pairwise nonlinear regression analysis (h2 coefficient). To study FC changes between parietal, frontal and temporal regions, for each patient, z-score values of 16 cortico-cortical interactions were obtained comparing h2 coefficients of pre-ictal, seizure onset and seizure propagation periods. Results We included 22 patients, 13 with “motor seizures” and 9 with “non-motor seizures”. Resective surgery was performed in 14 patients, 8 patients had a positive surgical outcome (Engel’s class I and II). During seizure onset period, a decrease of FC was observed and was significantly more important (in comparison with background period) in “motor” seizures. This was particularly observed between parietal operculum/post-central gyrus (OP/PoCg) and mesial temporal areas. During seizure propagation, a FC increase was significantly more important (in comparison with seizure onset) in “motor seizures”, in particular between lateral pre-motor (pmL) area and precuneus, pmL and superior parietal lobule (SPL) and between inferior parietal lobule (IPL) and supplementary motor area (SMA). Conclusions Our study shows that motor semiology in PLS is accompanied by an increase of FC between parietal and premotor cortices, significantly different than what is observed in PLS without motor semiology. Significance Our results indicate that preferential routes of coupling between parietal and premotor cortices are responsible for the prominent motor presentation during PLS.

International audience; In patients with epilepsy, alteration of awareness (AOA) during seizures is a disabling feature that can potentially lead to serious consequences such as falls and injuries. Regarding the neural mechanisms underlying AOA in focal seizures, some hypotheses have been put forward. In temporal lobe epilepsy, AOA has been related to the extension of the discharge to subcortical structures and to subsequent widespread inhibition (Blumenfeld and Taylor, 2003) or disturbed synchrony process (Bartolomei and Naccache, 2011) of the fronto-parietal association cortices. Thalamic stimulation was shown to be effective in reducing AOA (Gummadavelli et al., 2015). The medial pulvinar (PuM) is a thalamic nucleus often involved in focal seizures in different type of epilepsy (Pizzo et al., 2020). In a recent work (Filipescu et al., 2019), we observed that high frequency stimulation of the PuM during temporal lobe seizures could lead to improvement of awareness. Data from intracranial recordings in epileptic patients suggested that transition between conscious and non-conscious states during seizures was due to an excessive synchrony between the thalamus and associative cortices (Arthuis et al., 2009; Bartolomei and Naccache, 2011).

International audience; Purpose: Frontal seizures are organized according to anatomo-functional subdivisions of the frontal lobe. Prefrontal seizures have been the subject of few detailed studies to date. The objective of this study was to identify subcategories of prefrontal seizures based on seizure onset quantification and to look for semiological differences.Methods: Consecutive patients who underwent stereoelectroencephalography (SEEG) for drug-resistant prefrontal epilepsy between 2000 and 2018 were included. The different prefrontal regions investigated in our patients were dorsolateral prefrontal cortex (DLPFC), ventrolateral prefrontal cortex (VLPFC), dorsomedial prefrontal cortex (DMPFC), ventromedial prefrontal cortex (VMPFC), and orbitofrontal cortex (OFC). The seizure onset zone (SOZ) was determined from one or two seizures in each patient, using the epileptogenicity index (EI) method. The presence or absence of 16 clinical ictal manifestations was analyzed. Classification of prefrontal networks was performed using the k-means automatic classification method.Results: A total of 51 seizures from 31 patients were analyzed. The optimal clustering was 4 subgroups of prefrontal seizures: a "pure DLPF" group, a "pure VMPF" group, a "pure OFC" group, and a "global prefrontal" group. The first 3 groups showed a mean EI considered epileptogenic (>0.4) only in one predominant structure, while the fourth group showed a high mean EI in almost all prefrontal structures. The median number of epileptogenic structures per seizure (prefrontal or extrafrontal) was 5 for the "global prefrontal" group and 2 for the other groups. We found that the most common signs were altered consciousness, automatisms/stereotypies, integrated gestural motor behavior, and hyperkinetic motor behavior. We found no significant difference in the distribution of ictal signs between the different groups.Conclusion: Our study showed that although most prefrontal seizures manifest as a network of several anatomically distinct structures, we were able to determine a sublobar organization of prefrontal seizure onset with four groups.

Postictal generalized suppression (PGES) may be associated with SUDEP risk. We aimed to study metabolic changes onWe analyzed interictal brain metabolism in a group of 19 patients with widespread postictal suppression (PGES+) associated with SEEG-recorded GTCS. This group was compared to 25 patients without widespread suppression (PGES-) as defined by SEEG, matched for epilepsy localization and lateralization. Frequency of GTCS was observed to be higher in the PGES+ group (high risk group for SUDEP). Analysis of metabolic data was performed by statistical parametric mapping (SPM) on the whole-brain, and principal component analysis (PCA) on AAL (automated anatomical labeling) atlas.Statistical parametric mapping showed right temporal pole hypometabolism in the PGES+ group (T-score = 3.90; p 0.001; k = 185), in comparison to the PGES- group. Principal component analysis showed association between the metabolic values of certain regions of interest and PGES+/PGES- groups, confirmed by a significant difference (p 0.05) in the values of the right dorsal temporal pole and of the left temporal pole between the two groups. Principal component analysis showed two dimensions significantly related to the PGES+/PGES- partition, involving the following regions: right temporal pole, right parahippocampal gyrus, right Rolandic operculum, bilateral paracentral lobule, right precuneus, right thalamus, right caudate and pallidum, bilateral cerebellum, left temporal pole, left Heschl's gyrus, left calcarine region, and left caudate, with loss of connection in PGES+ patients. Metabolic differences were independent of epilepsy localization and lateralization and persisted after correction for GTCS frequency.Interictal metabolic changes within a predominantly right-sided network involving temporal lobe and connected cortical and subcortical structures were seen in patients with frequent GTCS presenting widespread postictal suppression.

International audience; Skin Conductance Biofeedback (SCB) is a non-invasive behavioral treatment for epilepsy based on modulation of Galvanic Skin Response (GSR). We evaluated changes in functional connectivity occurring after SCB. Six patients with drug-resistant temporal lobe epilepsy underwent monthly SCB sessions. For each patient, 10 min of resting-state magnetoencephalographic (MEG) recording were acquired before and after the first and the last SCB session. For each recording we computed the mean weighted phase lag index (WPLI) across all pair of MEG sensors. After SCB, two patients had consistent reduction of seizure frequency (>50 %). Connectivity analysis revealed a decrease of WPLI-beta band in the two responders and an increase of WPLI-alpha connectivity in all patients regardless of the clinical effect. Results suggest that reduction of WPLI-beta-low connectivity is related to the clinical response after SCB.

Objective Hyperkinetic epileptic seizures (HKS) are difficult to characterize and localize according to semiologic features. We propose a multicriteria scale to help visual analysis and report results of cerebral localization. Methods We assessed seizures from 37 patients with HKS, explored with stereoelectroencephalography during presurgical evaluation. We used a multicriteria scale (hyperkinetic seizure scale [HSS]) with 10 semiologic features, scored independently by two neurologists. The item scores were used to group seizures using the k-means method. Semiologic features were correlated with the seizure onset zone (SOZ) localization (temporal, prefrontal dorsolateral, prefrontal ventromesial, parietal, insular). Results Fifty-five seizures were analyzed, and each item of the HSS was compared between the two examiners with good interrater agreement (85.3%). Dystonia, integrated behavior, and bilateral or unilateral hyperkinetic movements were statistically significant according to localization. Three clusters were identified according to the HSS and correlated with different patterns of anatomic localization of SOZ. Cluster 1 was characterized clinically by asymmetric hyperkinetic movements associated with marked dystonia and vocalization. It mainly included parietal seizures. Cluster 2 was characterized by bilateral and symmetrical stereotyped hyperkinetic movements without dystonia. It represented half of temporal seizures and one-third of prefrontal seizures (dorsolateral). Cluster 3 was characterized by seizures with strong emotionality and vocalization with bilateral and symmetrical hyperkinetic movements and integrated behavior. It involved half of temporal seizures and a majority of prefrontal (ventromesial) seizures. Significance We propose a first attempt to quantify clinical patterns of HKS. The HSS may help to predict SOZ localization according to three main groups of hyperkinetic seizures.

ObjectiveTo determine the involvement of subcortical regions in human epilepsy by analyzing direct recordings from these regions during epileptic seizures using stereo-EEG (SEEG).MethodsWe studied the SEEG recordings of a large series of patients (74 patients, 157 seizures) with an electrode sampling the thalamus and in some cases also the basal ganglia (caudate nucleus, 22 patients; and putamen, 4 patients). We applied visual analysis and signal quantification methods (Epileptogenicity Index [EI]) to their ictal recordings and compared electrophysiologic with clinical data.ResultsWe found that in 86% of patients, thalamus was involved during seizures (visual analysis) and 20% showed high values of epileptogenicity (EI >0.3). Basal ganglia may also disclose high values of epileptogenicity (9% in caudate nucleus) but to a lesser degree than thalamus (p < 0.01). We observed different seizure onset patterns including low voltage high frequency activities. We found high values of thalamic epileptogenicity in different epilepsy localizations, including opercular and motor epilepsies. We found no difference between epilepsy etiologies (cryptogenic vs malformation of cortical development, p = 0.77). Thalamic epileptogenicity was correlated with the extension of epileptogenic networks (p = 0.02, ρ 0.32). We found a significant effect (p < 0.05) of thalamic epileptogenicity regarding the postsurgical outcome (higher thalamic EI corresponding to higher probability of surgical failure).ConclusionsThalamic involvement during seizures is common in different seizure types. The degree of thalamic epileptogenicity is a possible marker of the epileptogenic network extension and of postsurgical prognosis.

International audience; Patients suffering from drug-resistant temporal lobe epilepsy show substantial language deficits (i.e anomia) during their seizures and in the postictal period (postictal aphasia). Verbal impairments observed during the postictal period may be studied to help localizing the epileptogenic zone. These explorations have been essentially based on simple tasks focused on speech, thus disregarding the multi-modal nature of verbal communication, particularly the fact that, when speakers want to communicate, they often produce gestures of various kinds. Here, we propose an innovative procedure for testing postictal language and communication abilities, including the assessment of co-speech gestures. We provide a preliminary description of the changes induced on communication during postictal aphasia.We studied 21 seizures that induced postictal aphasia from 12 patients with drug-refractory epilepsy, including left temporal and left frontal seizures. The experimental task required patients to memorize a highly detailed picture and, briefly after, to describe what they had seen, thus eliciting a communicative meaningful monologue. This allowed comparing verbal communication in postictal and interictal conditions within the same individuals. Co-speech gestures were coded according to two categories: “Rhythmic” gestures, thought to be produced in support of speech building, and “illustrative” gestures, thought to be produced to complement the speech content. When postictal and interictal conditions were compared, there was decreased speech flow along with an increase of rhythmic gesture production at the expense of illustrative gesture production. The communication patterns did not differ significantly after temporal and frontal seizures, yet they were illustrated separately, owing to the clinical importance of the distinction, along with considerations of inter-individual variability. A contrast between rhythmic and illustrative gestures production is congruent with previous literature in which rhythmic gestures have been linked to lexical retrieval processes. If confirmed in further studies, such evidence for a facilitative role of co-speech gestures in language difficulties could be put to use in the context of multimodal language therapies.

Objectif : Etudier l’acceptabilite qu’ont les medecins generalistes (MG) du dossier medical partage (DMP), dans le contexte de la prise en charge des personnes sans chez-soi (PSCS).Methodes : Etude mixte sequentielle, qualitative puis quantitative. Pour la phase qualitative, des MG impliques dans la precarite ont ete interviewes par entretiens semi-diriges. Pour la phase quantitative 150 MG marseillais ayant une pratique typique de la medecine generale ont ete tires au sort puis interroges via un questionnaire. L’acceptabilite pratique et sociale du DMP etait quantifiee par echelles de Likert.Resultats : 19 MG ont ete interviewes pour la phase qualitative et 105 MG ont ete inclus (73 % de repondants) pour la phase quantitative. Les MG connaissaient mal le DMP. La moitie (52,5 %) des MG seraient prets a utiliser le DMP pour les PSCS. Il etait percu comme pouvant ameliorer la continuite des soins, sa qualite et sa securite pour les PSCS. L’interet du DMP etait percu superieur pour les PSCS que pour les patients en general, notamment sur le gain de temps envisage (p = 0,03). En revanche, le DMP etait mal connu, et les MG craignaient un detournement et une securisation insuffisante du stockage des donnees. Des limites specifiques aux PSCS etaient relevees, dont l’acces pratique au DMP pour les PSCS (carte vitale, acces internet).Conclusion : Le DMP pourrait etre une solution pour ameliorer la continuite des soins des PSCS. Il faut cependant adapter l’outil a la prise en charge des PSCS et informer les professionnels pour une utilisation effective.

Objective: High-frequency oscillations (HFOs) in intracerebral EEG (stereoencephalography, SEEG) are considered as better biomarkers of epileptogenic tissues than spikes. How this can be applied at the patient level remains poorly understood. We investigated how well the HFOs and the spikes can predict epileptogenic regions with a large spatial sampling at the patient level. Methods: We analyzed non-REM sleep SEEG recordings sampled at 2048 Hz of thirty patients. Ripples (R, 80-250 Hz), fast ripples (FR, 250-500 Hz) and spikes were automatically detected. Rates of these markers and several combinations – spikes co-occurring with HFOs or FRs and cross rate (Spk ⊗ HFO) – were compared to a quantified measure of the seizure onset zone (SOZ) by performing a receiver operating characteristic analysis for each patient individually. We used a Wilcoxon sign rank test corrected for false-discovery rate to assess whether a marker was better than the others for predicting the SOZ. Results: A total of 2930 channels was analyzed (median of 100 channels per patient). The HFOs or any of its variants were not statistically better than spikes. Only one feature, the cross-rate was better than all the other markers. Moreover, fast ripples, even though very specific, did not delineate all epileptogenic tissues. Interpretation: At the patient level, the performance of the HFOs is weakened by the presence of strong physiological HFO generators. Fast ripples are not sensitive enough to be the unique biomarker of epileptogenicity. Nevertheless, combining HFOs and spikes using our proposed measure –the cross rate– is a better strategy than using only one marker.

International audience; Anxiety and depression in epilepsy are strongly documented but post-traumatic stress disorder (PTSD) is underestimated and poorly known. We studied the links between psycho-traumagenic events (TE), onset of epilepsy, and severity of PTSD symptoms in patients with epilepsy. The study included 54 patients with epilepsy and 61 controls. We used validated questionnaires to screen for anxiety, depression, and PTSD symptoms and we conducted an interview to measure the prevalence of TE. We developed an original exploratory questionnaire to assess the presence of PTSD during interictal and peri-ictal periods. The results show that patients reported more exposure to a TE and presented significantly more severe PTSD symptoms than controls. Seventy-eight percent of patients (vs. 52% of controls) had been exposed to a TE, and 26% (vs. 7%) had a score above the diagnostic threshold of the PTSD scale. In addition, 18.6% of patients reported that their epilepsy began at the same time as they began to experience PTSD symptoms following a TE. Patients with high PTSD scores (above the threshold, n = 14) reported significantly more depression symptoms than patients without PTSD and reported PTSD symptoms both during the ictal and peri-ictal periods. Within the whole group of patients, anxiety (72%) and depression (33%) symptoms significantly correlated with PTSD symptoms reported by the scale. This study shows that patients with epilepsy have increased prevalence of self-reported PTSD symptoms. We describe the clinical picture specific to patients with epilepsy, which may include classical PTSD symptoms but also specific peri-ictal symptoms.

Background Magnetoencephalography allows defining non-invasively the spatio-temporal activation of brain networks thanks to source localization algorithms. A major difficulty of MNE and beamforming methods, two classically used techniques, is the definition of proper thresholds that allow deciding the extent of activated cortex. New method We investigated two strategies for computing a threshold, taking into account the difficult multiple comparison issue. The strategies were based either on parametric statistics (Bonferroni, FDR correction) or on empirical estimates (local FDR and a custom measure based on the survival function). Results We found thanks to the simulations that parametric methods based on the sole estimation of H 0 (Bonferroni, FDR) performed poorly, in particular in high SNR situations. This is due to the spatial leakage originating from the source localization methods, which give a ‘blurred’ reconstruction of the patch extension: the higher the SNR, the more this effect is visible. Comparison with existing methods Adaptive methods such as local FDR or our proposed ‘concavity threshold’ performed better than Bonferroni or classical FDR. We present an application to real data originating from auditory stimulation in MEG. Conclusion In order to estimate source extent, adaptive strategies should be preferred to parametric statistics when dealing with ‘leaking’ source reconstruction algorithms.

International audience; Neuroimaging biomarkers differ between patients with early-onset Alzheimer's disease (EOAD) and late-onset Alzheimer's disease (LOAD). Whether these changes reflect cognitive heterogeneity or differences in disease severity is still unknown. This study aimed at investigating changes in neuroimaging biomarkers, according to the age of onset of the disease, in mild amnestic Alzheimer's disease patients with positive amyloid biomarkers in cerebrospinal fluid. Both patient groups were impaired on tasks assessing verbal and visual recognition memory. EOAD patients showed greater executive and linguistic deficits, while LOAD patients showed greater semantic memory impairment. In EOAD and LOAD, hypometabolism involved the bilateral temporoparietal junction and the posterior cingulate cortex. In EOAD, atrophy was widespread, including frontotemporoparietal areas, whereas it was limited to temporal regions in LOAD. Atrophic volumes were greater in EOAD than in LOAD. Hypometabolic volumes were similar in the 2 groups. Greater extent of atrophy in EOAD, despite similar extent of hypometabolism, could reflect different underlying pathophysiological processes, different glucose-based compensatory mechanisms or distinct level of premorbid atrophic lesions.

International audience; No abstract available

The hippocampus and amygdala are key brain structures of the medial temporal lobe, involved in cognitive and emotional processes as well as pathological states such as epilepsy. Despite their importance, it is still unclear whether their neural activity can be recorded non-invasively. Here, using simultaneous intracerebral and magnetoencephalography (MEG) recordings in patients with focal drug-resistant epilepsy, we demonstrate a direct contribution of amygdala and hippocampal activity to surface MEG recordings. In particular, a method of blind source separation, independent component analysis, enabled activity arising from large neocortical networks to be disentangled from that of deeper structures, whose amplitude at the surface was small but significant. This finding is highly relevant for our understanding of hippocampal and amygdala brain activity as it implies that their activity could potentially be measured non-invasively.

Objective In focal epilepsies, the accurate delineation of the epileptogenic network is a fundamental step before surgery. For years, the relationship between the interictal epileptic spikes (defining the “irritative zone”, IZ) and the sites of seizure initiation (SOZ) has been a matter of debate. Methods Our goal was to investigate from intracerebral recordings (stereoelectroencephalography, SEEG) the distribution of interictal epileptic spikes (based on a spike frequency index, SI) and the topography of the SOZ (based on the Epileptogenicity Index, EI) in patients having focal neocortical epilepsies. Thirty-one patients were studied. A total of 539 brain regions were quantified in term of both spike generation (SI) and seizure initiation (EI). Results We found a 56% (18/32) rate of agreement between maximal EI and maximal SI values. When considering separately patients with focal cortical dysplasia (FCD), the proportion of patients with good concordance was ∼75% (15/20), whereas it was only 33% (4/12) in the non FCD group. Conclusions Our results show that a significant part of patients have some dissociation between regions showing pronounced spiking activity and those showing high epileptogenicity. e is clinically important. Significance For patients with these dissociations, other markers than spiking frequency remain to be investigated. In the FCD group, the good concordance between SI and EI confirms that the mapping of the irritative zone is clinically important.

Objectif Le role du sommeil dans la consolidation mnesique est reconnu et impliquerait un transfert de l’information de l’hippocampe au neocortex au cours du sommeil lent, grâce au couplage entre les ripples hippocampiques, les fuseaux thalamo-corticaux et les ondes lentes corticales. Le but de ce travail est d’etudier l’interaction de ces oscillations chez l’homme. Methodes Nous avons inclus huit patients atteints d’epilepsie focale pharmacodependante enregistres en stereo-electro-encephalographie avec : –une exploration ipsilaterale de l’hippocampe, le thalamus (pulvinar) et le gyrus frontal moyen ; –une frequence des pointes inferieure a 15/min. Nous avons calcule le grand-moyennage de l’analyse temps-frequence centre sur les ripples et sur les fuseaux, effectue une analyse de coherence inter-essai et calcule les co-occurrences entre ripples, entre fuseaux et les co-occurrences entre fuseaux et ripples au sein de chacune des regions. Resultats On retrouve des activites dans la bande de frequence des ripples centres sur le creux des fuseaux dans la region frontale, l’hippocampe et le thalamus. Des ondes lentes surviennent en phase avec les fuseaux dans les trois regions. Les fuseaux et les ripples co-occurrent de facon plus significative entre la region frontale et l’hippocampe. Les ripples et les fuseaux co-occurrent de facon plus significative dans l’hippocampe. Les ripples hippocampiques co-occurrent significativement avec les fuseaux frontaux. Conclusion Notre travail retrouve une interaction entre fuseaux et ripples au sein de l’hippocampe, du thalamus et de la region frontale.

Interictal stereotactic-EEG functional connectivity in refractory focal epilepsies Lagarde S, Roehri N, Lambert I, et al. Brain. 2018;141(10):2966-2980.Drug-refractory focal epilepsies are network diseases associated with functional connectivity alterations both during ictal and interictal periods. A large majority of studies on the interictal/resting state have focused on functional magnetic resonance imaging (MRI)-based functional connectivity. Few studies have used electrophysiology, despite its high-temporal capacities. In particular, stereotactic-electroencephalogram (EEG) is highly suitable to study functional connectivity because it permits direct intracranial electrophysiological recordings with relative large-scale sampling. Most previous studies in stereotactic-EEG have been directed toward temporal lobe epilepsy, which does not represent the whole spectrum of drug-refractory epilepsies. The present study aims at filling this gap, investigating interictal functional connectivity alterations behind cortical epileptic organization and its association with postsurgical prognosis. To this purpose, we studied a large cohort of 59 patients with malformation of cortical development explored by stereotactic-EEG with a wide spatial sampling (76 distinct brain areas were recorded, median of 13.2 per patient). We computed functional connectivity using nonlinear correlation. We focused on 3 zones defined by stereotactic-EEG ictal activity: the epileptogenic zone (EZ), the propagation zone (PZ), and the noninvolved zone. First, we compared within-zone and between-zones functional connectivity. Second, we analyzed the directionality of functional connectivity between these zones. Third, we measured the associations between functional connectivity measures and clinical variables, especially postsurgical prognosis. Our study confirms that functional connectivity differs according to the zone under investigation. We found: (1) a gradual decrease in the within-zone functional connectivity with higher values for EZ and PZ, and lower for noninvolved zones; (2) preferential coupling between structures of the EZ; (3) preferential coupling between EZ and PZ; and (4) poorer postsurgical outcome in patients with higher functional connectivity of non-involved zone (within-noninvolved zone, between noninvolved zone, and PZ functional connectivity). Our work suggests that, even during the interictal state, functional connectivity is reinforced within epileptic cortices (EZ and PZ) with a gradual organization. Moreover, larger functional connectivity alterations, suggesting more diffuse disease, are associated with poorer postsurgical prognosis. This is consistent with computational studies suggesting that connectivity is crucial in order to model the spatiotemporal dynamics of seizures. Dynamic brain network states in human generalized spike-wave discharges Tangwiriyasakul C, Perani S, Centeno M, et al. Brain. 2018;141(10):2981-2994.Generalized spike-wave discharges in idiopathic generalized epilepsy are conventionally assumed to have abrupt onset and offset. However, in rodent models, discharges emerge during a dynamic evolution of brain network states, extending several seconds before and after the discharge. In human idiopathic generalized epilepsy, simultaneous EEG and functional MRI shows cortical regions may be active before discharges, and network connectivity around discharges may not be normal. Here, in human idiopathic generalized epilepsy, we investigated whether generalized spike-wave discharges emerge during a dynamic evolution of brain network states. Using EEG-functional MRI, we studied 43 patients and 34 healthy control subjects. We obtained 95 discharges from 20 patients. We compared data from patients with discharges with data from patients without discharges and healthy controls. Changes in MRI (blood oxygenation level dependent) signal amplitude in discharge epochs were observed only at and after EEG onset, involving a sequence of parietal and frontal cortical regions then thalamus (P < .01, across all regions and measurement time points). Examining MRI signal phase synchrony as a measure of functional connectivity between each pair of 90 brain regions, we found significant connections (P < .01, across all connections and measurement time points) involving frontal, parietal and occipital cortex during discharges, and for 20 seconds after EEG offset. This network prominent during discharges showed significantly low synchrony (below 99% confidence interval for synchrony in this network in nondischarge epochs in patients) from 16 seconds to 10 seconds before discharges, then ramped up steeply to a significantly high level of synchrony 2 seconds before discharge onset. Significant connections were seen in a sensorimotor network in the minute before discharge onset. This network also showed elevated synchrony in patients without discharges compared to healthy controls (P = .004). During 6 seconds prior to discharges, additional significant connections to this sensorimotor network were observed, involving prefrontal, and precuneus regions. In healthy subjects, significant connections involved a posterior cortical network. In patients with discharges, this posterior network showed significantly low synchrony during the minute prior to discharge onset. In patients without discharges, this network showed the same level of synchrony as in healthy controls. Our findings suggest persistently high sensorimotor network synchrony, coupled with transiently (at least 1 minute) low posterior network synchrony, may be a state predisposing to generalized spike-wave discharge onset. Our findings also show that EEG onset and associated MRI signal amplitude change is embedded in a considerably longer period of evolving brain network states before and after discharge events.

To assess the acceptability for GPS to use the French shared Electronic Health Record (Dossier Médical Partagé, "DMP") when caring for Homeless People (HP).Mixed, sequential, qualitative-quantitative study. The qualitative phase consisted of semi-structured interviews with GPs involved in the care of HP. During the quantitative phase, questionnaires were sent to 150 randomized GPs providing routine healthcare in Marseille. Social and practical acceptability was studied by means of a Likert Scale.19 GPs were interviewed during the qualitative phase, and 105 GPs answered the questionnaire during the quantitative phase (response rate: 73%). GPs had a poor knowledge about DMP. More than half (52.5%) of GPs were likely to effectively use DMP for HP. GPs felt that the "DMP" could improve continuity, quality, and security of care for HP. They perceived greater benefits of the use the DMP for HP than for the general population, notably in terms of saving time (p = 0.03). However, GPs felt that HP were vulnerable and wanted to protect their patients; they worried about security of data storage. GPs identified specific barriers for HP to use DMP: most of them concerned practical access for HP to DMP (lack of social security card, or lack of tool for accessing internet).A shared electronic health record, such as the French DMP, could improve continuity of care for HP in France. GPs need to be better informed, and DMP functions need to be optimized and adapted to HP, so that it can be effectively used by GPs for HP.

Objectives We aimed to describe intracerebral aspects of postictal generalized electroencephalography suppression (PGES) following focal to bilateral tonic-clonic ("secondarily generalized tonic-clonic") seizures (GTCS) recorded using stereoelectroencephalographic (SEEG), and to correlate these with electroclinical features. Methods Three independent observers scored semiologic and SEEG features. Patient and epilepsy characteristics were collected. Descriptive statistics and multivariate analysis were performed. The operational definition of PGES on SEEG used strict criteria (absence of visible signal at 20 μV/mm amplitude, in all readable channels). Postictal regional suppression (RS) was identified if only a subset of implanted electrodes showed absence of signal. Results We evaluated 100 seizures in 52 patients. Interobserver agreement was good (κ 0.72 for clinical features and 0.73 for EEG features). PGES was present in 27 of 100 and RS without PGES present in 42 of 100 seizures. Region of RS included epileptogenic zone in 43 of 51 (86%). No effect of sampling (multilobar or bilateral exploration) was seen. Oral tonicity (mouth opening and/or tonic vocalization during the tonic phase of GTCS) was associated with the presence of PGES (P = 0.029; negative predictive value [NPV] 0.91). Bilateral upper limb extension during the tonic phase correlated with PGES (P = 0.041; NPV 0.85). Association of both oral tonicity and bilateral upper limb extension had a high NPV of 0.96. Significance SEEG recordings confirm true absence of signal during postictal EEG suppression. PGES is unlikely when both upper limb extension and oral tonicity are absent. We hypothesize that bilateral tonic seizure discharge at bulbar level brainstem regions is associated with the production of oral signs and may relate to mechanisms of PGES.

International audience; Resective surgery is a well-established treatment for pharmacoresistant frontal lobe epilepsy (FLE), but seizure outcome and prognostic indicators are poorly characterised and vary between studies. Objective: To study long-term seizure outcome and identify prognostic factors. Methods: We retrospectively analysed 42 FLE patients having undergone surgical resection, mostly preceded by invasive recordings with stereo-electroencephalography (SEEG). Post-surgical outcome up to 10 years' follow-up and prognostic indicators were analysed using Kaplan-Meier analysis, multivariate and conditional inference procedures. Results: At the time of last follow-up 57.1% of patients were seizure-free. The estimated chance of seizure freedom was 67% (95% CI 54-83) at 6 months, 59% (95% CI 46-76) at 1 year, 53% (95% CI 40-71) at 2 years and 46 % (95% CI 32-66) at 5 years. Most relapses (83%) occurred within the first 12 months. Multivariate analysis showed that completeness of resection of the epileptogenic zone (EZ) as defined by SEEG was the main predictor of seizure outcome. According to conditional inference trees, in patients with complete resection of the epileptogenic zone, focal cortical dysplasia as aetiology and focal EZ were positive prognostic indicators. No difference in outcome was found in patients with positive versus negative MRI. Conclusion: Surgical resection in drug-resistant FLE can be a successful therapeutic approach, even in the absence of neuroradiologically visible lesions. SEEG may be highly useful in both non-lesional and lesional FLE cases, since complete resection of the EZ as defined by SEEG is associated with better prognosis.

International audience; Objective Non-rapid eye movement (NREM) sleep is known to be a brain state associated with an activation of interictal epileptic activity. The goal of this work was to quantify topographic changes occurring during NREM sleep in comparison with wakefulness. Method We studied intracerebral recordings of 20 patients who underwent stereo-electroencephalography (SEEG) during presurgical evaluation for pharmacoresistant focal epilepsy. We measured the number of interictal spikes (IS) and quantified the co-occurrence of IS between brain regions during 1hour of NREM sleep and 1hour of wakefulness. Co-occurrence is a method to estimate IS networks based on a temporal concordance between IS of different brain regions. Each studied region was labeled as seizure-onset zone (SOZ), propagation zone (PZ), or not involved region (NIR). Results During NREM sleep, the number of interictal spikes significantly increased in all regions (mean of 68%). This increase was higher in medial temporal regions than in other regions, whether involved in the SOZ. Spike co-occurrence increased significantly in all regions during NREM sleep in comparison with wakefulness but was greater in neocortical regions. Spike co-occurrence in medial temporal regions was not higher than in other regions, suggesting that the increase of the number of spikes in this region was in great part a local effect. Significance This study demonstrated that medial temporal regions show a greater propensity to spike production or propagation during NREM sleep compared to other brain regions, even when the medial temporal lobe is not involved in the SOZ.

Objectif L’objectif de ce travail est d’etudier l’impact des pointes epileptiques hippocampiques grâce a des enregistrements intracrâniens (stereoencephalographie, SEEG) sur les capacites de consolidation mnesique a long terme (plusieurs jours), en etudiant egalement l’effet sur les fuseaux du sommeil hippocampiques. Methodes Un total de 20 patients explores en SEEG dans le cadre du bilan prechirurgical d’une epilepsie focale pharmaco-resistante, avec une implantation hippocampique uni ou bilaterale, ont ete inclus. Ils ont passe des tests de memoire 48 h apres l’implantation des electrodes puis un rappel une semaine plus tard. Les analyses ont ete effectuees sur la nuit suivant la premiere session de tests mnesiques : detection des pointes epileptiques hippocampiques et detection des fuseaux de sommeil hippocampiques. Resultats On retrouve une correlation negative entre la frequence des pointes au cours du sommeil lent et les performances mnesiques a une semaine. Il existe une correlation negative entre la frequence des pointes epileptiques au cours du sommeil lent et la frequence des fuseaux hippocampiques. Neanmoins, aucune correlation n’est retrouvee entre la frequence des fuseaux de sommeil hippocampiques et les performances mnesiques a une semaine. Conclusion Ces resultats suggerent que les pointes epileptiques hippocampiques survenant au cours du sommeil lent interferent avec les processus responsables de la consolidation de la memoire a long terme. Les fuseaux hippocampiques ne semblent pas directement associes aux processus de consolidation mnesique a long terme.

Defining the roles of heterotopic and normotopic cortex in the epileptogenic networks in patients with nodular heterotopia is challenging. To elucidate this issue, we compared heterotopic and normotopic cortex using quantitative signal analysis on stereoelectroencephalography (SEEG) recordings.Clinically relevant biomarkers of epileptogenicity during ictal (epileptogenicity index; EI) and interictal recordings (high-frequency oscillation and spike) were evaluated in 19 patients undergoing SEEG. These biomarkers were then compared between heterotopic cortex and neocortical regions. Seizures were classified as normotopic, heterotopic, or normoheterotopic according to respective values of quantitative analysis (EI ≥0.3).A total of 1,246 contacts were analyzed: 259 in heterotopic tissue (heterotopic cortex), 873 in neocortex in the same lobe of the lesion (local neocortex), and 114 in neocortex distant from the lesion (distant neocortex). No significant difference in EI values, high-frequency oscillations, and spike rate was found comparing local neocortex and heterotopic cortex at a patient level, but local neocortex appears more epileptogenic (p0.001) than heterotopic cortex analyzing EI values at a seizure level. According to EI values, seizures were mostly normotopic (48.5%) or normoheterotopic (45.5%); only 6% were purely heterotopic. A good long-term treatment response was obtained in only two patients after thermocoagulation and surgical disconnection.This is the first quantitative SEEG study providing insight into the mechanisms generating seizures in nodular heterotopia. We demonstrate that both the heterotopic lesion and particularly the normotopic cortex are involved in the epileptogenic network. This could open new perspectives on multitarget treatments, other than resective surgery, aimed at modifying the epileptic network.

High-frequency oscillations (HFOs) in intracerebral EEG (stereoelectroencephalography; SEEG) are considered as better biomarkers of epileptogenic tissues than spikes. How this can be applied at the patient level remains poorly understood. We investigated how well HFOs and spikes can predict epileptogenic regions with a large spatial sampling at the patient level.We analyzed non-REM sleep SEEG recordings sampled at 2,048Hz of 30 patients. Ripples (Rs; 80-250Hz), fast ripples (FRs; 250-500Hz), and spikes were automatically detected. Rates of these markers and several combinations-spikes co-occurring with HFOs or FRs and cross-rate (Spk⊗HFO)-were compared to a quantified measure of the seizure onset zone (SOZ) by performing a receiver operating characteristic analysis for each patient individually. We used a Wilcoxon signed-rank test corrected for false-discovery rate to assess whether a marker was better than the others for predicting the SOZ.A total of 2,930 channels was analyzed (median of 100 channels per patient). The HFOs or any of its variants were not statistically better than spikes. Only one feature, the cross-rate, was better than all the other markers. Moreover, fast ripples, even though very specific, were not delineating all epileptogenic tissues.At the patient level, the performance of HFOs is weakened by the presence of strong physiological HFO generators. Fast ripples are not sensitive enough to be the unique biomarker of epileptogenicity. Nevertheless, combining HFOs and spikes using our proposed measure-the cross-rate-is a better strategy than using only one marker. Ann Neurol 2018;83:84-97.

International audience; Objectives: The study of intracerebral electroencephalography (EEG) seizure-onset patterns is crucial to accurately define the epileptogenic zone and guide successful surgical resection. It also raises important pathophysiologic issues concerning mechanisms of seizure generation. Until now, several seizure-onset patterns have been described using distinct recording methods (subdural, depth electrode), mostly in temporal lobe epilepsies or with heterogeneous neocortical lesions. Methods: We analyzed data from a cohort of 53 consecutive patients explored by stereoelectroencephalography (SEEG) and with pathologically confirmed malforma-tion of cortical development (MCD; including focal cortical dysplasia [FCD] and neu-rodevelopmental tumors [NDTs]). Results: We identified six seizure-onset patterns using visual and time-frequency analysis: low-voltage fast activity (LVFA); preictal spiking followed by LVFA; burst of poly-spikes followed by LVFA; slow wave/DC shift followed by LVFA; theta/alpha sharp waves; and rhythmic spikes/spike-waves. We found a high prevalence of patterns that included LVFA (83%), indicating nevertheless that LVFA is not a constant characteristic of seizure onset. An association between seizure-onset patterns and histologic types was found (p = 001). The more prevalent patterns were as follows: (1) in FCD type I LVFA (23.1%) and slow wave/baseline shift followed by LVFA (15.4%); (2) in FCD type II burst of polyspikes followed by LVFA (31%), LVFA (27.6%), and preictal spiking followed by LVFA (27.6%); (3) in NDT, LVFA (54.5%). We found that a seizure-onset pattern that included LVFA was associated with favorable postsurgical outcome, but the completeness of the EZ resection was the sole independent predictive variable. Significance: Six different seizure-onset patterns can be described in FCD and NDT. Better postsurgical outcome is associated with patterns that incorporate LVFA.

The brain at rest exhibits a spatio-temporally rich dynamics which adheres to systematic behaviours that persist in task paradigms but appear altered in disease. Despite this hypothesis, many rest state paradigms do not act directly upon the rest state and therefore cannot confirm hypotheses about its mechanisms. To address this challenge, we combined transcranial magnetic stimulation (TMS) and electroencephalography (EEG) to study brain’s relaxation toward rest following a transient perturbation. Specifically, TMS targeted either the medial prefrontal cortex (MPFC), i.e. part of the Default Mode Network (DMN) or the superior parietal lobule (SPL), involved in the Dorsal Attention Network. TMS was triggered by a given brain state, namely an increase in occipital alpha rhythm power. Following the initial TMS-Evoked Potential, TMS at MPFC enhances the induced occipital alpha rhythm, called Event Related Synchronisation, with a longer transient lifetime than TMS at SPL and a higher amplitude. Our findings show a strong coupling between MPFC and the occipital alpha power. Although the rest state is organized around a core of resting state networks, the DMN functionally takes a special role among these resting state networks.

Summary Objective Rasmussen's encephalitis (RE) is a severe chronic inflammatory brain disease affecting one cerebral hemisphere and leading to drug-resistant epilepsy, progressive neurologic deficit, and unilateral brain atrophy. Hemispherotomy remains the gold standard treatment but causes permanent functional impairment. No standardized medical treatment protocol currently exists for patients prior to indication of hemispherotomy, although some immunotherapies have shown partial efficacy with functional preservation but poor antiseizure effect. Some studies suggest a role for tumor necrosis factor alpha (TNF-α) in RE pathophysiology. Methods We report an open-label study evaluating the efficacy and the safety of anti-TNF-α therapy (adalimumab) in 11 patients with RE. The primary outcome criterion was the decrease of seizure frequency. The secondary outcome criteria were neurologic and cognitive outcomes and existence of side effects. Results Adalimumab was introduced with a median delay of 31 months after seizure onset (range 1 month to 16 years), and follow-up was for a median period of 18 months (range 9–54 months). There was a significant seizure frequency decrease after adalimumab administration (from a median of 360 to a median of 32 seizures per quarter, p ≤ 0.01). Statistical analysis showed that adalimumab had a significant intrinsic effect (p < 0.005) independent from disease fluctuations. Five patients (45%) were found to have sustained improvement over consecutive quarters in seizure frequency (decrease of 50%) on adalimumab. Three of these five patients also had no further neurocognitive deterioration. Adalimumab was well tolerated. Significance Our study reports efficacy of adalimumab in terms of seizure frequency control. In addition, stabilization of functional decline occurred in three patients. This efficacy might be particularly relevant for atypical slowly progressive forms of RE, in which hemispherotomy is not clearly indicated. Due to our study limitations, further studies are mandatory to confirm these preliminary results.

International audience; Interpretation of hemodynamic responses in epilepsy is hampered by an incomplete understanding of the underlying neurovascular coupling, especially the contributions of excitation and inhibition. We made simultaneous multimodal recordings of local field potentials (LFPs), firing of individual neurons, blood flow, and oxygen level in the somatosensory cortex of anesthetized rats. Epileptiform discharges induced by bicuculline injections were used to trigger large local events. LFP and blood flow were robustly coupled, as were LFP and tissue oxygen. In a parametric linear model, LFP and the baseline activities of cerebral blood flow and tissue partial oxygen tension contributed significantly to blood flow and oxygen responses. In an analysis of recordings from 402 neurons, blood flow/tissue oxygen correlated with the discharge of putative interneurons but not of principal cells. Our results show that interneuron activity is important in the vascular and metabolic responses during epileptiform discharges.

Introduction Cancer population studies require reliable and complete baseline data, which should theoretically be available by collecting histopathology records. The completeness of such a collection was evaluated using capture–recapture analysis based on three data sources concerning breast and colorectal cancers over an identical period and within the same geographical area. Method The total number of breast and colon cancer cases was estimated using capture–recapture analysis based on the number of cases which were common or not between sources recording screened, diagnosed and treated cancers in the French Alpes Maritimes district. Result The estimated total number of new cases of breast cancer diagnosed among Alpes Maritimes residents women aged 50–75 was 791 (95% CI: 784–797) in 2008. Of these 791 cases, 729 were identified through histopathology records, thus amounting to 92.2% completeness (95% CI: 91.5–93.0%). The total estimated number of new cases of colorectal cancer diagnosed among Alpes Maritimes residents aged 50–75 was 527 (95% CI: 517–536). Of these 527 cases, 481 were identified through histopathology records, thus amounting to 91.3% completeness (95% CI: 89.7–93.0%). Conclusion The estimated completeness of cancer records collected from histopathology laboratories was higher than 90% for new cases of breast and colorectal cancer within the age range concerned by the screening programme. A verified and validated histopathology data collection may be useful for cancer population studies.

Situation du probleme. L’analyse des reseaux sociaux est une methode de description et de modelisation de la structure relationnelle d’un ensemble d’acteurs. L’objectif de ce travail est d’analyser les relations entre les differents etablissements du systeme de sante, a travers un exemple : celui de la prise en charge de l’infarctus du myocarde dans la region Provence Alpes Cote-d’Azur (PACA). Methodologie. Etude retrospective de tous les sujets hospitalises pour un infarctus aigu du myocarde dans tous les etablissements de sante de la region PACA entre janvier et juin 2000. Une analyse descriptive a consiste a realiser un graphe decrivant les transferts entre etablissements, a calculer les indicateurs de centralite et de prestige des etablissements, a determiner quels sont les sous-groupes cohesifs (cliques) puis a decrire la densite du reseau hospitalier. Resultats. Le nombre total d’etablissements de sante ayant pris en charge un infarctus du myocarde est de 78. Le nombre de patients hospitalises pour un infarctus du myocarde est de 2049. Le nombre total de transferts est de 867. Le nombre de cliques mis en evidence est de 51. Vingt-neuf etablissements ne participent a aucune clique. Parmi les 49 etablissements participant a des sous-groupes, 50 % contribuent a plus de 2 cliques. Huit etablissements participent a plus de 8 cliques. Le maximum est une participation a 12 cliques. La densite du reseau hospitalier est de 0,12. Conclusions. L’analyse des reseaux sociaux constitue donc un champ de recherche ouvert en Sante Publique. Cette methode pourrait etre appliquee dans l’evaluation des reseaux de sante et le fonctionnement d’un hopital.

The management of craniopharyngioma in children represents a challenging problem. If radical excision is recommended by many authors as the initial treatment, in some cases, particularly in recurrent tumours, other methods (gamma knife surgery and intracystic bleomycin) can be very useful. Even if craniopharyngioma is a benign tumour, recurrences are frequent, and the aim of our study was to analyse our results, to try to determine some prognostic factors of recurrences and to discuss about a new strategy concerning the initial management of these tumours. Forty-seven children with craniopharyngioma were treated in the Department of Pediatric Neurosurgery. All of the patients, but five children treated by intracystic bleomycin, underwent a surgical resection of the tumour as initial treatment with the goal of achieving gross total removal (GTR) of the tumour. Two children had radiotherapy and gamma knife treatment, respectively, following surgery for a tumoural residue. All the children had a magnetic resonance imaging (MRI) study 3 months after surgery to evaluate the results of the initial treatment. Using statistical analysis, some prognostic factors (age, sex, location, aspect, size of the tumour and result of the first MRI) have been studied. Forty-two children were operated on, but one died in the immediate postoperative period from a major stroke due to carotid spasm. GTR, defined as the absence of residue on the first MRI control, was achieved in 27 children (65.8%), but 7 patients (25.9%) presented recurrence. Subtotal removal (STR) was obtained in 14 children (34.2%), but 9 patients (64.3%) developed a recurrence defined as the growth of the residual tumour with or without clinical symptoms. Five children having a small- or moderate-size cystic craniopharyngioma were treated using one-stage (three cases) or two-stage (two cases) intracystic bleomycin and any presented recurrence. All the prognostic factors studied, except one (presence of a residue on the first MRI control), do not have a statistical significance. Craniopharyngioma in children remains a formidable tumour, and regardless of whatever progress made in their management, the incidence of recurrences is still elevated and severe sequelae can be observed. There are no prognostic factors among those studied concerning the recurrences of these tumours except the quality of the exeresis confirmed by the first postoperative MRI.

Purpose To study refraction variations during the day in eyes with intrastromal corneal ring segments (ICRS) to correct low myopia. Setting Monticelli Clinic, Marseille, France Methods Thirteen eyes with ICRS were included in the study; the ICRS was explanted from 3 eyes because of undercorrection. The minimum follow-up in all eyes was 1 year. The same observer measured refraction and keratometry at 9:00 am , 1:00 pm , and 7:00 pm with the same autokeratorefractometer. To validate the analysis method, these eyes were compared with a group of emmetropic control eyes that had not had surgery and with a group of eyes that had photorefractive keratectomy for a similar degree of myopia. All measurements were done under the same conditions. Results After 1 year, the ICRS eyes showed a tendency toward an evening myopic shift. This was confirmed by the objective keratometry study, which showed variations closely correlated with the myopia observed. These phenomena were not observed in the other groups. Conclusion The ICRS had satisfactory predictability in eyes with up to –3.50 diopters of myopia. However, the evening myopic shift appeared similar to that observed after radial keratotomy.

Recognition of different kinds of visual stimuli was studied in a patient who acquired apperceptive visual agnosia after a bilateral occipitotemporal lesion which partially spared the primary visual cortex. Impairment in recognising static objects perceived visually sharply contrasts with the relatively well preserved ability to recognise objects from gestures illustrating their use, and to recognise actions shown in line drawings. It is suggested that the occipitoparieto-frontal pathway is involved in the recognition of actions, and in the recognition of objects when sensorimotor experience is evoked.

The occurrence of anomia specifically affecting the ability to name animals is described in three patients. This deficit is contrasted with their capacity to name actions and tools. It is suggested that it is easier to access the names of 'operative' items, which were learned through both visual and sensorimotor experience, than the names of 'figurative' items, which were primarily learned through the visual modality. This hypothesis is consistent with the infero-temporal location of brain damage in these patients. Their ability to retrieve knowledge about operative items is assumed to be due to the sparing of the occipito-parietal area. Because the impairment also involves the recognition of animals, the likely locus of damage is the semantic component of the processing system.

Primary and secondary unresponsiveness to meglumine has long been described in human visceral leishmaniasis. However, no studies have been performed to elucidate if these therapeutic failures were due to strain variability in meglumine sensitivity or were related to host factors. We have studied the in vitro sensitivity of 37 strains of Leishmania infantum isolated from 23 patients (11 human immunodeficiency virus-infected and 12 immunocompetent patients) with visceral leishmaniasis. Sensitivity tests were performed by infecting murine macrophages with Leishmania parasites and culturing them in medium containing different concentrations of meglumine. For each test we calculated a 50% effective dose (ED50) corresponding to the meglumine concentration at which 50% of the Leishmania parasites survived. In vitro results were strongly correlated to immediate clinical outcome. All strains requiring an ED50 of >70 microg/ml were related to therapeutic failures, whereas all strains requiring an ED50 of