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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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

SummaryObjective Frontal lobe seizures are difficult to characterize according to semiologic and electrical features. We wished to establish whether different semiologic subgroups can be identified and whether these relate to anatomic organization. Methods We assessed all seizures from 54 patients with frontal lobe epilepsy that were explored with stereoelectroencephalography (SEEG) during presurgical evaluation. Semiologic features and concomitant intracerebral EEG changes were documented and quantified. These variables were examined using Principal Component Analysis and Cluster Analysis, and semiologic features correlated with anatomic localization. Results Four main groups of patients were identified according to semiologic features, and correlated with specific patterns of anatomic seizure localization. Group 1 was characterized clinically by elementary motor signs and involved precentral and premotor regions. Group 2 was characterized by a combination of elementary motor signs and nonintegrated gestural motor behavior, and involved both premotor and prefrontal regions. Group 3 was characterized by integrated gestural motor behavior with distal stereotypies and involved anterior lateral and medial prefrontal regions. Group 4 was characterized by seizures with fearful behavior and involved the paralimbic system (ventromedial prefrontal cortex ± anterior temporal structures). The groups were organized along a rostrocaudal axis, representing bands within a spectrum rather than rigid categories. The more anterior the seizure organization, the more likely was the occurrence of integrated behavior during seizures. Distal stereotypies were associated with the most anterior prefrontal localizations, whereas proximal stereotypies occurred in more posterior prefrontal regions. Significance Meaningful categorization of frontal seizures in terms of semiology is possible and correlates with anatomic organization along a rostrocaudal axis, in keeping with current hypotheses of frontal lobe hierarchical organization. The proposed electroclinical categorization offers pointers as to the likely zone of organization of networks underlying semiologic production, thus aiding presurgical localization. Furthermore, analysis of ictal motor behavior in prefrontal seizures, including stereotypies, leads to deciphering the cortico-subcortical networks that produce such behaviors.

Music is a sound structure of remarkable acoustical and temporal complexity. Although it cannot denote specific meaning, it is one of the most potent and universal stimuli for inducing mood. How the auditory and limbic systems interact, and whether this interaction is lateralized when feeling emotions related to music, remains unclear. We studied the functional correlation between the auditory cortex (AC) and amygdala (AMY) through intracerebral recordings from both hemispheres in a single patient while she listened attentively to musical excerpts, which we compared to passive listening of a sequence of pure tones. While the left primary and secondary auditory cortices (PAC and SAC) showed larger increases in gamma-band responses than the right side, only the right side showed emotion-modulated gamma oscillatory activity. An intra- and inter-hemisphere correlation was observed between the auditory areas and AMY during the delivery of a sequence of pure tones. In contrast, a strikingly right-lateralized functional network between the AC and the AMY was observed to be related to the musical excerpts the patient experienced as happy, sad and peaceful. Interestingly, excerpts experienced as angry, which the patient disliked, were associated with widespread de-correlation between all the structures. These results suggest that the right auditory-limbic interactions result from the formation of oscillatory networks that bind the activities of the network nodes into coherence patterns, resulting in the emergence of a feeling.

UNLABELLED Three-dimensional concepts underlie various congenital foot deformities in the midfoot. We wondered whether the first cuneiform osteotomy, usually indicated for forefoot correction, had an effect on the hindfoot. We retrospectively studied 18 patients (31 feet) with metatarsus adductus and varus who had a biplane first cuneiform osteotomy between 1994 and 2001. No patients had associated malformations or neuromuscular disease. All had persistent pain and functional complaints for at least 2 years before surgery, and all had a minimum followup of 2 years. Group A (13 feet) with forefoot adduction without hindfoot valgus had an isolated first cuneiform osteotomy. Group B (18 feet) with slight forefoot adduction, hindfoot valgus, and supination after hindfoot valgus correction had first cuneiform osteotomy and a subtalar arthrodesis. At 5 years mean followup we evaluated multiple measurements on preoperative and followup weightbearing radiographs. Complementary demographic information and clinical patient information were collected. First cuneiform osteotomy was associated with architectural changes in hindfoot bone angles. This finding suggests new surgical approaches. LEVEL OF EVIDENCE Therapeutic Study. Level IV (Case series). See the Guidelines for Authors for a complete description of levels of evidence.

Polyhandicapped children are extremely limited by severe mental retardation, motor deficiency, perception disability and expression troubles. So pain is very difficult to assess in these patients. We have developed a specific scale for rapid evaluation of pain based on the observation of their behaviour. A first questionnaire listing 22 items was elaborated by physicians and nurses on the basis of their clinical experience. The first part of our study was designed to select the most pertinent items in order to define a final scale for simple and reliable everyday use. The second part of our study was designed to demonstrate the construct validity and the psychometric qualities and to determine the threshold of decision of the 10-item final scale. This tool seems to be sensitive and reliable enough to assess pain in severely cerebrally palsied children and young adults.