Étude Électrophysiologique en Stéréo-Électroencéphalographie (SEEG) de la Connectivité Fonctionnelle Inter-Ictale dans les Épilepsies Focales Pharmacorésistantes : le modèle des Malformations du Développement Cortical

Les épilepsies focales pharmacorésistantes (EPR) sont des maladies de réseaux, avec des altérations de connectivité fonctionnelle (CF) durant les périodes ictale & interictale. La plupart des études sur la CF de la période interictale utilisent l’IRM fonctionnelle. Peu d’études ont exploité les avantages de la stéréo-électroencéphalographie (SEEG) : très bonne résolution temporelle, enregistrement intracrânien direct et échantillonnage spatial relativement large. Les quelques études en SEEG ont concerné les EPR temporales qui ne reflètent pas l’ensemble du spectre des EPR. Notre étude avait pour but de combler ce manque en investiguant les altérations de CF qui sous-tendent l’organisation des cortex épileptiques et leur association avec le pronostic chirurgical.Pour cela, nous avons étudié une large cohorte de 59 patients avec malformation du développement cortical, explorés par SEEG. Nous avons calculé : la CF avec une corrélation non-linéaire (h2), et la centralité intermédiaire (CI). Nous nous sommes concentré sur 3 sous-réseaux définis par l’activité ictale : zone épileptogène (ZE), zone de propagation (ZP), zone non impliquée (ZNI). Nous avons analysé : 1) la CF intra-zone et inter-zone, 2) la CI de ces zones, 3) la directionalité de la CF entre ces zones, 4) les associations entre mesures de CF et variables cliniques dont le pronostic chirurgical.Notre travail confirme que la CF diffère selon les sous-réseaux. Nous avons trouvé : 1) des valeurs plus hautes de CF intra-zone dans ZE et ZP par rapport à ZNI, 2) un couplage préférentiel à l’intérieur de la ZE, 3) un couplage préférentiel entre ZE et ZP, 4) un pronostic chirurgical défavorable chez les patients avec une CF plus élevée dans ZNI (CF intra-ZNI, inter ZNI-ZP, et CI de ZNI). Notre travail suggère une CF renforcée dans les cortex épileptiques (ZE et ZP) avec une organisation graduelle selon l’épileptogénicité. De plus, des altérations plus larges de CF sont associées à un pronostic chirurgical plus défavorable

Encéphalite de Rasmussen : hypothèses physiopathologiques et traitement médical

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Seizure onset patterns and functional inter-ictal connectivity in focal epilepsies : SEEG studies

Dans cette thèse, nous avons étudié des patients avec épilepsie focale résistante aux traitements antiépileptiques explorés en stéréo-EEG. Nos objectifs étaient : 1) de décrire les patterns de début de crise (SOP) et analyser leur association avec les données cliniques (notamment étiologie, pronostic post-chirurgie, organisation de la zone épileptogène) ; 2) étudier la connectivité fonctionnelle (CF) interictale et rechercher des différences de connectivité selon l'épileptogénicité des structures.Concernant les SOP, nous avons montré que: environ 20% des SOP n’incluent pas de décharge rapide (< 12hz), certains SOP sont associés à des étiologies particulières (ex : bouffée de polypointes suivies d’une décharge rapide et dysplasie corticale focale), certains SOP sont associés au type d’organisation spatiale de la zone épileptogène (ex : ondes lentes / DC shift suivi d’une décharge rapide et organisation en réseau), le pronostic post-chirurgical est meilleur en cas de SOP incluant une décharge rapide de bas voltage.Concernant la CF inter-ictale, nous avons montré : une CF plus élevées entre les zones épileptogènes et entre les zones de propagation qu’entre les zones non impliquées lors des crises, un couplage préférentiel des zones épileptogènes entre elles et avec les zones de propagation, un pronostic post-opératoire moins bon en cas de CF plus élevée dans les zones non impliquéesEn résumé, nous avons donc montré que 1) les SOP sont liés aux caractéristiques du patients (notamment étiologie) et au pronostic post-chirurgical ; 2) la CF interictale est renforcée dans les zones épileptiques à distance des crises et pourrait être un indicateur du pronostic post-chirurgical.In this thesis, we studied patients with focal epilepsy resistant to antiepileptic treatments explored in stereo-EEG, in order to be able to offer them curative epilepsy surgery. Our objectives were: 1) to describe the seizure onset patterns (SOP) and analyse their association with clinical data (aetiology, prognosis, organisation of the epileptogenic zone); 2) to study interictal functional connectivity and to look for differences in connectivity according to the epileptogenicity of the structures. Regarding the SOP, we demonstrated that: About 20% of the SOP did not include a rapid discharge (< 12hz), some SOP were associated with particular aetiology (e.g. burst of poly-spikes followed by a rapid discharge and focal cortical dysplasia), some SOP were associated with the type of spatial organization of the epileptogenic zone (e.g. slow waves / DC shift followed by a rapid discharge and network organization), the post-operative prognosis is better in case of SOP including a rapid low voltage discharge.Regarding inter-ictal functional connectivity, we demonstrated: a higher functional connectivity between epileptogenic areas and between the propagation area, than between non-involved areas in the seizure; preferential coupling of the epileptogenic zones between them and with the propagation zones • A poorer post-surgical outcome in case of higher functional connectivity of the noninvolved areasOverall, we thus demonstrated that 1) seizure onset patterns were related to patient characteristics (notably the aetiology) and post-surgical prognosis; 2) interictal functional connectivity is enhanced in epileptic areas and could be an indicator of post-surgical prognosis

Apport de la tomographie par émission de positons (TEP) cérébrale dans les encéphalites dysimmunitaires

International audienceDysimmune encephalitis are frequent and disabling pathologies with efficacious treatments (immunotherapy). Evocative clinical signs are: rapid progressive evolution, seizure, movement disorder, psychiatric troubles, memory defect, dysautonomia and hyponatremia. Classical ancillary test: magnetic resonance imaging (MRI) and standard cerebro-spinal fluid (CSF) analysis can be normal. In this context, the cerebral positron emission tomography (PET) is helpful for the diagnosis. More often reported patterns are: association of hyper- and hypo-metabolism; fronto-temporal hyper-metabolism/parieto-occipital hypo-metabolism gradient (anti-N-methyl-D-aspartate receptor [NMDAR] encephalitis); temporal and basal ganglia hyper-metabolism (anti-leucine-rich glioma inactivated protein 1 [LGI1] encephalitis); temporal hyper-metabolism (other limbic encephalitis); parieto-occipital ± basal ganglia hypo-metabolism (neurolupus); unihemispheric diffuse hypo-metabolism (Rasmussen encephalitis). The diagnosis could require research of specific antibodies. Finally, the cerebral PET is also useful during the follow-up: treatment's efficacy (improvement of metabolism), relapse (aggravation of metabolism's alteration), and evaluation of possible sequelae.Les encéphalites dysimmunitaires sont des pathologies fréquentes et pourvoyeuses de handicap, pour lesquelles il existe des traitements efficaces (immunothérapies). Certains signes cliniques sont évocateurs : évolution rapidement progressive, crise d’épilepsie, mouvements anormaux, troubles psychiatriques, troubles mnésiques, dysautonomie, hyponatrémie. Les examens classiques, notamment l’imagerie par résonance magnétique (IRM) et les analyses standard du liquide céphalo-rachidien (LCR), peuvent être pris en défaut. Dans ce contexte, la tomographie par émission de positons (TEP) cérébrale a un grand intérêt pour le diagnostic. Les patterns retrouvés sont : association d’hypo- et d’hypermétabolisme, gradient hypermétabolisme fronto-temporal/hypométabolisme pariéto-occipital (encéphalites anti-N-methyl-D-aspartate receptor [NMDAR]), hypermétabolisme temporal et des ganglions de la base (encéphalite anti-leucine-rich glioma inactivated protein 1 [LGI1]), hypermétabolisme temporal (autres encéphalites limbiques), hypométabolismes pariéto-occipital ± des ganglions de la base (neurolupus), hypométabolisme unihémisphérique diffus (encéphalite de Rasmussen). La confirmation diagnostique pourra nécessiter la recherche d’anticorps spécifique (sérum/LCR). La TEP cérébrale est aussi utile au cours du suivi : efficacité du traitement (amélioration du métabolisme), rechute (aggravation des altérations du métabolisme) et évaluation d’éventuelles séquelles

Medical treatment of Rasmussen's Encephalitis: A systematic review

International audienceRasmussen's encephalitis (RE) is a severe, rare, chronic inflammatory brain disease resulting in drug-resistant epilepsy and progressive destruction of one hemisphere with loss of neurological function. RE is associated with a deterioration of background electroencephalography (EEG) activity, a progressive atrophy on magnetic resonance imaging (MRI) imaging and an extensive positron emission tomography hypometabolism over the affected hemisphere. RE is an immune-mediated disease, with a predominant role of CD8+ T cytotoxic cells, microglial cells, and activation of inflammasome pathway. The diagnosis of RE is based on clinical (intractable epilepsy and neurological deterioration), electrophysiological (unilateral EEG slowing) and MRI (hemiatrophy) criteria. Antiseizure medications are generally unable to stop seizures. The most effective procedure is hemispherotomy (surgical disconnection of one cerebral hemisphere), but this is associated with permanent motor and neurological deficits. Treatments targeting the immune system are recommended especially in the early stages of the disease or in patients with slow disease progression and mild deficits and/or not eligible for surgery. Based on the pathophysiology, several immunotherapies have been tried in RE (none exhaustively: corticosteroid, intravenous immunoglobulins, tacrolimus, azathioprine, adalimumab, mycophenolate mofetil, natalizumab). However, only small cohorts have been reported without comparative study. In this review, we will summarise some pathophysiological mechanisms of RE, before reporting the literature data concerning immunotherapies. We then discuss the limitations of these studies and the prospects for further research

Insular interictal positron emission tomography hypometabolism in patients with ictal asystole

International audienceWe aimed to explore brain area(s) involved in the generation of ictal asystole (IA) by analyzing the interictal positron emission tomography (PET) metabolism of patients with IA recorded by video-electroencephalography or video-stereo-electroencephalography. We identified in our cohort of focal epilepsy patients who had undergone presurgical evaluation those who had a recorded period of IA of more than 3 s. We investigated the anatomometabolic changes (interictal 18 F-fluorodeoxyglucose PET) of these patients in comparison with (1) healthy subjects with similar age and sex distribution (n = 19) using whole-brain voxel-based analysis (p-voxel < .001, p-cluster < .05, uncorrected) and (2) patients without IA with similar age and seizure onset zone (n = 55). We found 12 patients with IA. Epilepsy was mainly temporal (four right temporal mesial, four bitemporal, two left temporal lateral, one right temporal lateral, and one right temporal "plus"). Seven patients had negative magnetic resonance imaging. Whole-brain statistical analysis of PET imaging was performed at the voxel level, showing that in comparison to healthy subjects and to epileptic patients without IA, a hypometabolism in the right posterior insula characterized epileptic patients with IA. Our study suggests involvement of the right posterior insula-a part of the central autonomic network-in the pathophysiological mechanism of IA

Interictal functional connectivity in focal refractory epilepsies investigated by intracranial EEG

International audienceFocal epilepsies are diseases of neuronal excitability affecting macroscopic networks of cortical and subcortical neural structures. These networks ("epileptogenic networks") can generate pathological electrophysiological activities during seizures but also between seizures (interictal period). Many works attempt to describe these networks by using quantification methods, particularly based on the estimation of statistical relationships between signals produced by brain regions, namely Functional connectivity (FC). FC has been shown to be greatly altered during seizures and in the immediate peri-ictal period. An increasing number of studies have shown that FC is also altered during the interictal period depending on the degree of epileptogenicity of the structures. Furthermore, connectivity values could be correlated with other clinical variables including surgical outcome. This leads to a conceptual change and to consider epileptic areas as both hyperexcitable and abnormally connected. These data open the door to the use of interictal FC as a marker of epileptogenicity and as a complementary tool for predicting the effect of surgery. In this article, we will review the available data concerning interictal FC estimated from iEEG in focal epilepsies and discuss it in the light of data obtained from other modalities (EEG, MEG, MRI) and modelling studies

How Can a Focal Seizure Lead to a Dacrystic Behavior? A Case Analyzed with Functional Connectivity in Stereoelectroencephalography

We present a case of a patient with focal non-motor emotional seizures with dacrystic expression in the context of drug-resistant magnetic resonance imaging negative epilepsy. The pre-surgical evaluation suggested a hypothesis of a right fronto-temporal epileptogenic zone. Stereoelectroencephalography recorded dacrystic seizures arising from the right anterior operculo-insular ( pars orbitalis) area with secondary propagation to temporal and parietal cortices during the dacrystic behavior. We analyzed functional connectivity during the ictal dacrystic behavior and found an increase of the functional connectivity within a large right fronto-temporo-insular network, broadly similar to the “emotional excitatory” network. It suggests that focal seizure, potentially, from various origins but leading to disorganization of these physiological networks may generate dacrystic behavior

VIDEO-EEG ILLUSTRATION OF TRANSIENT EPISODES OF LOSS OF CONSCIOUNESS CORRELATED WITH PLATEAU-WAVES DUE TO INTRACRANIAL HYPERTENSION

International audienceA 54-year-old woman, with relapsing Mantle B-cell Lymphoma, was admitted for recurrent unresponsive episodes. During video-EEG recording, patient became transitory unresponsive for 12 minutes with starring and brachiofacial automatisms (video), with correlated diffuse EEG delta activity that resolved spontaneously, without epileptic discharge, cardiac arrhythmia, or hypotension (figure). No intracranial lesion existed on neuroimaging. Lumbar puncture revealed increased CSF pressure and infiltrating lymphomatous cells, confirming a diagnosis of leptomeningeal metastases. Transient neurological events can be linked to increased intracranial pressure generating a decrease of cerebral perfusion and EEG "plateau-waves" 1-5. EEG allow to distinguish this entity from differential diagnoses

Early onset motor semiology in seizures triggered by cortical stimulation during SEEG

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