Equipe épilepsie adulte

Service de neurologie fonctionnelle et épileptologie

Le service de neurologie fonctionnelle et d’épileptologie est spécialisé dans la prise en charge des patients souffrant d’épilepsie et dans les explorations fonctionnelles du cerveau et de la moelle épinière via la réalisation d’électroencéphalogrammes et de potentiels évoqués.

neurologie fonctionnelle-neurophysio
Pr Sylvain RHEIMS

Pr Sylvain RHEIMS

Coordinateur de l’équipe (CRNL Tiger)

Autres membres de l’équipe:

    – Pr J. Jung (CRNL Eduwell)

    – Dr A. Richard-Morna (CRNL Tiger)

    – Dr H. Catenoix (CRNL Tiger)

    – Dr S. Boulogne (CRNL Tiger)

    – Dr A. Montavont (CRNL Tiger)

    – Dr N. André-Obadia (CRNL Neuropain)

    – Mme V. Guinet (CRNL Tiger)

Principales Collaborations:

    – HCL: Epilepsie enfant; neurochirurgie de l’épilepsie, hypnologie, génétique de l’épilepsie

    – Centres de recherche Lyon: CRNL, SBRI (C. Heinrich), PGNM (G. Lesca)

Thématiques

Les thématiques de recherche sont centrées autour des activités expertales du service, et plus particulièrement en épileptologie et en neurosciences cognitives grâce aux enregistrements intracérébraux réalisés chez les patients bénéficiant d’une SEEG. Ces activités s’appuient sur l’expertise synergique du service de Neurologie Fonctionnelle et d’Epileptologie et du service de Neurochirurgie Fonctionnelle (Pr Haegelen et Pr Guenot) ainsi qu’à des collaborations étroites avec le service d’épileptologie pédiatrique, le service d’hyponologie (Pr Peter-Derex) et le service de génétique clinique (Pr Lesca). L’ensemble des praticiens titulaires avec une expertise épileptologique sont ainsi rattachés à une équipe de recherche au sein du centre de recherche en neurosciences de Lyon (CNRL, INSERM U1028/CNRS UMR 5292). De plus, le service de Neurologie Fonctionnelle et d’Epileptologie accueille une des plateformes recherche commune HCL-CRNL, la plateforme « enregistrements intracérébraux» (S. Rheims, J. Jung, O. Bertrand et JP Lachaux).

Notre projet s’articule autour de :

  1. La problématique des comorbidités associées aux épilepsies et plus spécifiquement:
    • Les troubles cognitifs associées aux épilepsies de l’enfant, de l’adulte et chez le sujet âgé (Dr Richard-Mornas)
    • Le risque de mort soudaine inattendue dans l’épilepsie (SUDEP). Cette thématique a été particulièrement développé autour des cohortes nationales prospectives coordonnées par notre service et des approches translationnelles avec l’équipe TIGER du CRNL (Pr S. Rheims, Dr L. Bezin). Cette démarche se poursuit à l’échelle européenne, en particulier dans le syndrome de Dravet
  2. L’analyse de l’organisation des réseaux épileptiques, via l’analyse des données des patients bénéficiant d’une exploration avec électrodes intracérébrales ainsi que la poursuite de la validation de l’utilité clinique de la MEG et en EEG haute résolution (Pr J. Jung)
  3. Une implication régulière dans l’évaluation de nouvelles molécules dans l’épilepsie, depuis l’épilepsie nouvellement diagnostiqué à l’état de mal réfractaire et aux épilepsies rares. Ceci s’appuie en particulier sur les nombreux travaux de l’équipe autour des problématiques posées par le design des essais thérapeutiques en épileptologie (Pr S. Rheims), travaux qui ont contribué aux évolutions de des recommandations de la FDA et de l’EMA dans le design des essais

L’ensemble de ces activités s’intègrent dans l’activité du Centre Nationale de Référence des Epilepsies Rares (CREER) et du réseau européen de référence EPICARE

Projets principaux en cours

  1. PHRC ENALEPSIE : Efficacy of Naloxone in reducing postictal central respiratory dysfunction in patients with epilepsy. A multicenter double-blind placebo controlled trial. Role: PI
  2. RHU EPINOV : Improving EPilepsy surgery management and progNOsis using Virtual brain technology (EPINOV). Role: Partner
  3. ERANET NEURON : Neurodevelopmental impact of epilepsy on autonomic function in Dravet Syndrome (AUTONOMIC). Role PI
  4. PHRC EPIMEEG : cliquez ici pour plus d’informations.
  5. PHRC EPIMNESIE : cliquez ici pour plus d’informations.

Publications

  1. Functional connectivity and epileptogenicity of nodular heterotopias: A single-pulse stimulation study
    Boulogne S, Pizzo F, Chatard B, Roehri N, Catenoix H, Ostrowsky-Coste K, Giusiano B, Guenot M, Carron R, Bartolomei F, Rheims S

Epilepsia (2022) — Résumé

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Objective: 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.

2. Neuromodulation in epilepsy: state-of-the-art approved therapies
Ryvlin P, Rheims S, Hirsch LJ, Sokolov A, Jehi L

Lancet Neurol (2021) — Résumé

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Three neuromodulation therapies have been appropriately tested and approved in refractory focal epilepsies: vagus nerve stimulation (VNS), deep brain stimulation of the anterior nucleus of the thalamus (ANT-DBS), and closed-loop responsive neurostimulation of the epileptogenic zone or zones. These therapies are primarily palliative. Only a few individuals have achieved complete freedom from seizures for more than 12 months with these therapies, whereas more than half have benefited from long-term reduction in seizure frequency of more than 50%. Implantation-related adverse events primarily include infection and pain at the implant site. Intracranial haemorrhage is a frequent adverse event for ANT-DBS and responsive neurostimulation. Other stimulation-specific side-effects are observed with VNS and ANT-DBS. Biomarkers to predict response to neuromodulation therapies are not available, and high-level evidence to aid decision making about when and for whom these therapies should be preferred over other antiepileptic treatments is scant. Future studies are thus needed to address these shortfalls in knowledge, approve other forms of neuromodulation, and develop personalised closed-loop therapies with embedded machine learning. Until then, neuromodulation could be considered for individuals with intractable seizures, ideally after the possibility of curative surgical treatment has been carefully assessed and ruled out or judged less appropriate.

3. Dynamics of hippocampus and orbitofrontal cortex activity during arousing reactions from sleep: An intracranial electroencephalographic study
Ruby P, Eskinazi M, Bouet R, Rheims S, Peter-Derex L

Hum Brain Mapp (2021) — Résumé

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Sleep is punctuated by transient elevations of vigilance level called arousals or awakenings depending on their durations. Understanding the dynamics of brain activity modifications during these transitional phases could help to better understand the changes in cognitive functions according to vigilance states. In this study, we investigated the activity of memory-related areas (hippocampus and orbitofrontal cortex) during short (3 s to 2 min) arousing reactions detected from thalamic activity, using intracranial recordings in four drug-resistant epilepsy patients. The average power of the signal between 0.5 and 128 Hz was compared across four time windows: 10 s of preceding sleep, the first part and the end of the arousal/awakening, and 10 s of wakefulness. We observed that (a) in most frequency bands, the spectral power during hippocampal arousal/awakenings is intermediate between wakefulness and sleep whereas frontal cortex shows an early increase in low and fast activities during non-rapid-eye-movement (NREM) sleep arousals/awakenings; (b) this pattern depends on the preceding sleep stage with fewer modifications for REM than for non-REM sleep arousal/awakenings, potentially reflecting the EEG similarities between REM sleep and wakefulness; (c) a greater activation at the arousing reaction onset in the prefrontal cortex predicts longer arousals/awakenings. Our findings suggest that hippocampus and prefrontal arousals/awakenings are progressive phenomena modulated by sleep stage, and, in the neocortex, by the intensity of the early activation. This pattern of activity could underlie the link between sleep stage, arousal/awakening duration and restoration of memory abilities including dream recall.

4. Interpreting deep learning models for epileptic seizure detection on EEG signals
Gabeff V, Teijeiro T, Zapater M, Cammoun L, Rheims S, Ryvlin P, Atienza D

Artif Intell Med (2021) — Résumé

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Three neuromodulation therapies have been appropriately tested and approved in refractory focal epilepsies: vagus nerve stimulation (VNS), deep brain stimulation of the anterior nucleus of the thalamus (ANT-DBS), and closed-loop responsive neurostimulation of the epileptogenic zone or zones. These therapies are primarily palliative. Only a few individuals have achieved complete freedom from seizures for more than 12 months with these therapies, whereas more than half have benefited from long-term reduction in seizure frequency of more than 50%. Implantation-related adverse events primarily include infection and pain at the implant site. Intracranial haemorrhage is a frequent adverse event for ANT-DBS and responsive neurostimulation. Other stimulation-specific side-effects are observed with VNS and ANT-DBS. Biomarkers to predict response to neuromodulation therapies are not available, and high-level evidence to aid decision making about when and for whom these therapies should be preferred over other antiepileptic treatments is scant. Future studies are thus needed to address these shortfalls in knowledge, approve other forms of neuromodulation, and develop personalised closed-loop therapies with embedded machine learning. Until then, neuromodulation could be considered for individuals with intractable seizures, ideally after the possibility of curative surgical treatment has been carefully assessed and ruled out or judged less appropriate.

5. Anatomical dissociation of intracerebral signals for reward and punishment prediction errors in humans
Gueguen MCM, Lopez-Persem A, Billeke P, Lachaux JP, Rheims S, Kahane P, Minotti L, David O, Pessiglione M, Bastin J

Nat Commun (2021) — Résumé

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Whether maximizing rewards and minimizing punishments rely on distinct brain systems remains debated, given inconsistent results coming from human neuroimaging and animal electrophysiology studies. Bridging the gap across techniques, we recorded intracerebral activity from twenty participants while they performed an instrumental learning task. We found that both reward and punishment prediction errors (PE), estimated from computational modeling of choice behavior, correlate positively with broadband gamma activity (BGA) in several brain regions. In all cases, BGA scaled positively with the outcome (reward or punishment versus nothing) and negatively with the expectation (predictability of reward or punishment). However, reward PE were better signaled in some regions (such as the ventromedial prefrontal and lateral orbitofrontal cortex), and punishment PE in other regions (such as the anterior insula and dorsolateral prefrontal cortex). These regions might therefore belong to brain systems that differentially contribute to the repetition of rewarded choices and the avoidance of punished choices.

6. Attention deficit/hyperactivity disorder and epilepsy
Rheims S, Auvin S

Curr Opin Neurol (2021) — Résumé

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Purpose of review: Attention deficit/hyperactivity disorder (ADHD) is a frequent comorbidity in patients with epilepsy and is associated with important psychosocial and academic consequences. Evidence are now available to guide diagnosis and treatment of patients with both ADHD and epilepsy. Recent findings: The prevalence of ADHD varies from 12 to 39% in patients with newly diagnosed epilepsy to 70% in drug-resistant epilepsy. The diagnosis of ADHD requires parent-validated and teacher-validated rating scales, based on the Diagnostic and Statistical Manual of Mental Disorders (DSM)-IV and DSM-V, to confirm the information in the rating scales by interviewing parents and to exclude other causes of symptoms. Treatment with methylphenidate is associated with clinically significant improvement of ADHD symptoms in 60-75% of patients. Recent data reinforce the hypothesis that ADHD medications do not increase risk of seizures, even in patients with epilepsy. Beyond pharmacological management, experts have recommended to include multidisciplinary involvement in transition clinics for patients with both comorbid ADHD and epilepsy. Summary: Management of ADHD in patients with epilepsy requires implementation of evidence-based data in clinical practice both for diagnosis and treatment. Currently, there is no specific treatment of ADHD associated with epilepsy and its treatment is based on the usual treatments of ADHD, with reassuring data about their safety in epilepsy.

7. Neural mechanisms resolving exploitation-exploration dilemmas in the medial prefrontal cortex
Domenech P, Rheims S, Koechlin E

Science (2020) — Résumé

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Everyday life often requires arbitrating between pursuing an ongoing action plan by possibly adjusting it versus exploring a new action plan instead. Resolving this so-called exploitation-exploration dilemma involves the medial prefrontal cortex (mPFC). Using human intracranial electrophysiological recordings, we discovered that neural activity in the ventral mPFC infers and tracks the reliability of the ongoing plan to proactively encode upcoming action outcomes as either learning signals or potential triggers to explore new plans. By contrast, the dorsal mPFC exhibits neural responses to action outcomes, which results in either improving or abandoning the ongoing plan. Thus, the mPFC resolves the exploitation-exploration dilemma through a two-stage, predictive coding process: a proactive ventromedial stage that constructs the functional signification of upcoming action outcomes and a reactive dorsomedial stage that guides behavior in response to action outcomes.

8. Seizure outcome and use of antiepileptic drugs after epilepsy surgery according to histopathological diagnosis: a retrospective multicentre cohort study
Lamberink HJ, Otte WM, Blümcke I, Braun KPJ; European Epilepsy Brain Bank writing group; study group; European Reference Network EpiCARE

Lancet Neuro (2020) — Résumé

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Background Surgery is a widely accepted treatment option for drug-resistant focal epilepsy. A detailed analysis of longitudinal postoperative seizure outcomes and use of antiepileptic drugs for different brain lesions causing epilepsy is not available. We aimed to analyse the association between histopathology and seizure outcome and drug freedom up to 5 years after epilepsy surgery, to improve presurgical decision making and counselling. Methods In this retrospective, multicentre, longitudinal, cohort study, patients who had epilepsy surgery between Jan 1, 2000, and Dec 31, 2012, at 37 collaborating tertiary referral centres across 18 European countries of the European Epilepsy Brain Bank consortium were assessed. We included patients of all ages with histopathology available after epilepsy surgery. Histopathological diagnoses and a minimal dataset of clinical variables were collected from existing local databases and patient records. The primary outcomes were freedom from disabling seizures (Engel class 1) and drug freedom at 1, 2, and 5 years after surgery. Proportions of individuals who were Engel class 1 and drug-free were reported for the 11 main categories of histopathological diagnosis. We analysed the association between histopathology, duration of epilepsy, and age at surgery, and the primary outcomes using random effects multivariable logistic regression to control for confounding.

9. A Prospective Cohort Study to Identify Clinical, Biological, and Imaging Features That Predict the Etiology of Acute Encephalitis
Le Maréchal M, Mailles A, Seigneurin A, Tattevin P, Stahl JP, Épaulard O, Scientific Committee and Investigators Group

Clin Infect Dis (2021) — Résumé

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Background: New diagnostic tools have been developed to improve the diagnosis of infectious encephalitis. Using a prospective cohort of encephalitis patients, our objective was to identify possible clusters of patients with similar patterns among encephalitis of unknown cause (EUC) and to describe to what extent a patient’s initial presentation may be predictive of encephalitis etiology, particularly herpes simplex virus (HSV) and varicella-zoster virus (VZV). Methods: The National Cohort of Infectious Encephalitis in France is an ongoing prospective cohort study implemented in France in 2016. Patients who present with documented or suspected acute infectious encephalitis were included. Focusing on the variables that describe the initial presentation, we performed a factor analysis of mixed data (FAMD) to investigate a pattern of association between the initial presentation of a patient and the etiologic pathogen.

10. Four core properties of the human brain valuation system demonstrated in intracranial signals
Lopez-Persem A, Bastin J, Petton M, Abitbol R, Lehongre K, Adam C, Navarro V, Rheims S, Kahane P, Domenech P, Pessiglione M

Nat Neurosci (2020) — Résumé

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Estimating the value of alternative options is a key process in decision-making. Human functional magnetic resonance imaging and monkey electrophysiology studies have identified brain regions, such as the ventromedial prefrontal cortex (vmPFC) and lateral orbitofrontal cortex (lOFC), composing a value system. In the present study, in an effort to bridge across species and techniques, we investigated the neural representation of value ratings in 36 people with epilepsy, using intracranial electroencephalography. We found that subjective value was positively reflected in both vmPFC and lOFC high-frequency activity, plus several other brain regions, including the hippocampus. We then demonstrated that subjective value could be decoded (1) in pre-stimulus activity, (2) for various categories of items, (3) even during a distractive task and (4) as both linear and quadratic signals (encoding both value and confidence). Thus, our findings specify key functional properties of neural value signals (anticipation, generality, automaticity, quadraticity), which might provide insights into human irrational choice behaviors.

11. Cysts associated with intramedullary ependymomas of the spinal cord: clinical, MRI and oncological features
Dauleac C, Messerer R, Obadia-Andre N, Afathi M, Barrey CY

J Neurooncol (2019) — Résumé

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Purpose: Few published articles have explicitly focused on cysts associated with intramedullary (IM) ependymomas. The objective was to assess the clinical, MRI, and oncological results of patients operated for an IM ependymoma associated with a cystic portion. Methods: During the study period, 23 IM tumors resected were cystic ependymomas. The modified McCormick scale was used to assess the neurological function of patients. The diagnosis of cystic spinal cord tumor was made on preoperative MRI.