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Mania is characterized by affective and cognitive alterations, with heightened external and self-awareness that are opposite to the alteration of awareness during epileptic seizures. Electrical stimulations carried out routinely during stereotactic intracerebral EEG (SEEG) recordings for presurgical evaluation of epilepsy may represent a unique opportunity to study the pathophysiology of such complex emotional-behavioral phenomenon, particularly difficult to reproduce in experimental setting. We investigated SEEG signals-based functional connectivity between different brain regions involved in emotions and in consciousness processing during a manic state induced by electrical stimulation in a patient with drug-resistant focal epilepsy. The stimulation inducing manic state and an asymptomatic stimulation of the same site, as well as a seizure with alteration of awareness (AOA) were analyzed. Functional connectivity analysis was performed by measuring interdependencies (nonlinear regression analysis based on the h2 coefficient) between broadband SEEG signals and within typical sub-bands, before and after stimulation, or before and during the seizure with AOA, respectively. Stimulation of the right lateral prefrontal cortex induced a manic state lasting several hours. Its onset was associated with significant increase of broadband-signal functional coupling between the right hemispheric limbic nodes, the temporal pole and the claustrum, whereas significant decorrelation between the right lateral prefrontal and the anterior cingulate cortex was observed in theta-band. In contrast, ictal alteration of awareness was associated with increased broadband and sub-bands synchronization within and between the internal and external awareness networks, including the anterior and middle cingulate, the mesial and lateral prefrontal, the inferior parietal and the temporopolar cortex. Our data suggest the existence of network- and frequency-specific functional connectivity patterns during manic state. A transient desynchronization of theta activity between the external and internal awareness network hubs is likely to increase awareness, with potential therapeutic effect.

Introduction Over the past 20 years, Vagus Nerve Stimulation (VNS) has become one of the tools for surgical treatment of patients with refractory cryptogenic epilepsy. The objective of this study was to determine the feasibility of implanting a Vagus Nerve Stimulation in ambulatory patients with chronic epilepsy. Patients and methods VNS procedure was consecutively performed in outpatient surgery between November 2016 and November 2018 in patients with refractory epilepsy. The main endpoints were complications, prolonged hospitalization and readmission during the first postoperative month. This information was collected by retrospective analysis of clinical files. Results Of the 22 patients included, the majority were autonomous (77%) with only 5 institutionalized patients. Retrospective analysis revealed a single complication of temporary dysphonia (4.5%) and an unplanned hospitalisation for immediate post-operative vomiting (4.5%). No readmissions were observed during the postoperative month but an emergency room visit for generalized seizure disorder was reported for one patient. Conclusion The outpatient implantation of VNS in patients with epilepsy is a valid strategy for 95% of patients.

Objective Self-limited focal epilepsies of childhood (SFEC) are amongst the best defined and most frequent epilepsy syndromes affecting children with usually normal developmental milestones. They include core syndromes such as Rolandic epilepsy or “ Benign ” epilepsy with Centro-Temporal Spikes and the benign occipital epilepsies, the early onset Panayiotopoulos syndrome and the late-onset Gastaut type. Atypical forms exist for all of them. Atypical Rolandic epilepsies are conceptualized as belonging to a continuum reaching from the “benign” RE to the severe end of the Landau-Kleffner (LKS) and Continuous Spike-Waves during Sleep syndromes (CSWS). GRIN2A has been shown to cause the epilepsy-aphasia continuum that includes some patients with atypical Rolandic epilepsy with frequent speech disorders, LKS and CSWS. In the present study, we searched novel genes causing SFEC with typical or atypical presentations. Methods Exome sequencing was performed in 57 trios. Patients presented with typical or atypical SFEC, negative for GRIN2A pathogenic variant. Results We found rare candidate variants in 20 patients. Thirteen had occurred de novo and were mostly associated to atypical Rolandic Epilepsy. Two of them could be considered as disease related: a null variant in GRIN2B and a missense variant in CAMK2A. Others were considered good candidates, including a substitution affecting a splice site in CACNG2 and missense variants in genes encoding enzymes involved in chromatin remodeling. Significance Our results further illustrate the fact that atypical SFEC are more likely to have Mendelian inheritance than typical SFEC.

A 40-year-old woman with a drug-resistant focal epilepsy underwent cerebral FDG PET in phase 1 presurgical epilepsy study. MRI essentially showed multiple periventricular nodular heterotopias. The stereoelectroencephalography coupled to MRI and FDG PET helped to define the anatomofunctional correlation of the epileptogenic zone network. This procedure brought to light 3 distinct patterns of FDG consumption, corresponding to different anatomoelectroclinical features. This pattern was already found in a previous FDG PET reflecting a "stable" permanent intralesional intercritical stereoelectroencephalography activity, an electrical "signature" of the lesion. Finally, functional imaging improved thermocoagulation in this patient and emphasized the use of FDG in drug-resistant epilepsy.

International audience; Cause of complex dyskinesia remains elusive in some patients. A homozygous missense variant leading to drastic decrease of PDE2A enzymatic activity was reported in one patient with childhood-onset choreodystonia preceded by paroxysmal dyskinesia and associated with cognitive impairment and interictal EEG abnormalities. Here, we report three new cases with biallelic PDE2A variants identified by trio whole-exome sequencing. Mitochondria network was analyzed after Mitotracker™ Red staining in control and mutated primary fibroblasts. Analysis of retrospective video of patients' movement disorder and refinement of phenotype was carried out. We identified a homozygous gain of stop codon variant c.1180C>T; p.(Gln394*) in PDE2A in siblings and compound heterozygous variants in young adult: a missense c.446C>T; p.(Pro149Leu) and splice-site variant c.1922+5G>A predicted and shown to produce an out of frame transcript lacking exon 22. All three patients had cognitive impairment or developmental delay. The phenotype of the two oldest patients, aged 9 and 26, was characterized by childhood-onset refractory paroxysmal dyskinesia initially misdiagnosed as epilepsy due to interictal EEG abnormalities. The youngest patient showed a proven epilepsy at the age of 4 months and no paroxysmal dyskinesia at 15 months. Interestingly, analysis of the fibroblasts with the biallelic variants in PDE2A variants revealed mitochondria network morphology changes. Together with previously reported case, our three patients confirm that biallelic PDE2A variants are a cause of childhood-onset refractory paroxysmal dyskinesia with cognitive impairment, sometimes associated with choreodystonia and interictal baseline EEG abnormalities or epilepsy.

International audience; Stereoelectroencephalography (SEEG) was designed and developed in the 1960s in France by J. Talairach and J. Bancaud. It is an invasive method of exploration for drug-resistant focal epilepsies, offering the advantage of a tridimensional and temporally precise study of the epileptic discharge. It allows anatomo-electrical correlations and tailored surgeries. Whereas this method has been used for decades by experts in a limited number of European centers, the last ten years have seen increasing worldwide spread of its use. Moreover in current practice, SEEG is not only a diagnostic tool but also offers a therapeutic option, i.e., thermocoagulation. In order to propose formal guidelines for best clinical practice in SEEG, a working party was formed, composed of experts from every French centre with a large SEEG experience (those performing more than 10 SEEG per year over at least a 5 year period). This group formulated recommendations, which were graded by all participants according to established methodology. The first part of this article summarizes these within the following topics: indications and limits of SEEG; planning and management of SEEG; surgical technique; electrophysiological technical procedures; interpretation of SEEG recordings; and SEEG-guided radio frequency thermocoagulation. In the second part, those different aspects are discussed in more detail by subgroups of experts, based on existing literature and their own experience. The aim of this work is to present a consensual French approach to SEEG, which could be used as a basic document for centers using this method, particularly those who are beginning SEEG practice. These guidelines are supported by the French Clinical Neurophysiology Society and the French chapter of the International League Against Epilepsy.

Objective Within a complex systems biology perspective, we wished to assess whether hippocampi with established neuropathological features have distinct metabolome. Apparently normal hippocampi with no signs of sclerosis (noHS), were compared to hippocampal sclerosis (HS) type 1 (HS1) and/or type 2 (HS2). Hippocampus metabolome from patients with epilepsy-associated neuroepithelial tumors (EANTs), namely, gangliogliomas (GGs) and dysembryoplastic neuroepithelial tumors (DNTs), was also compared to noHS epileptiform tissue. Methods All patients underwent standardized temporal lobectomy. We applied 1 H high-resolution magic angle spinning nuclear magnetic resonance (HRMAS NMR) spectroscopy to 48 resected human hippocampi. NMR spectra allowed quantification of 21 metabolites. Data were analyzed using multivariate analysis based on mutual information. Results Clear distinct metabolomic profiles were observed between all studied groups. Sixteen and 18 expected metabolite levels out of 21 were significantly different for HS1 and HS2, respectively, when compared to noHS. Distinct concentration variations for glutamine, glutamate, and N-acetylaspartate (NAA) were observed between HS1 and HS2. Hippocampi from GG and DNT patients showed 7 and 11 significant differences in metabolite concentrations when compared to the same group, respectively. GG and DNT had a clear distinct metabolomic profile, notably regarding choline compounds, glutamine, glutamate, aspartate, and taurine. Lactate and acetate underwent similar variations in both groups. Significance HRMAS NMR metabolomic analysis was able to disentangle metabolic profiles between HS, noHS, and epileptic hippocampi associated with EANT. HRMAS NMR metabolomic analysis may contribute to a better identification of abnormal biochemical processes and neuropathogenic combinations underlying mesial temporal lobe epilepsy.

Objective Autosomal dominant sleep-related hypermotor epilepsy (ADSHE) is characterized by hypermotor seizures and may be caused by gain-of-function mutations affecting the nicotinic acetylcholine receptor (nAChR). Benefit from nicotine consumption has been reported in adult patients with this disorder. For the first time, the effect of transdermal nicotine is evaluated in children. Methods Transdermal nicotine was applied to three boys, two aged 10 years (7 mg/24 h) and one six years (3.5 mg/24 h). Autosomal dominant sleep-related hypermotor epilepsy was caused by the p.S280F-CHRNA4 (cholinergic receptor, nicotinic, alpha polypeptide 4) mutation. The children suffered from frequent, persistent nocturnal seizures and had developed educational and psychosocial problems. Seizure frequency and cognitive and behavioral parameters were assessed before and after treatment. Results A striking seizure reduction was reported soon after treatment onset. Hypermotor seizures disappeared; only sporadic arousals, sometimes with minor motor elements, were observed. Psychometric testing documented improvement in cognitive domains such as visuospatial ability, processing speed, memory, and some areas of executive functions. Significance Nicotine appears to be a mechanistic treatment for this specific disorder, probably because of desensitization of the mutated receptors. It may control seizures resistant to conventional drugs for epilepsy and impact socioeducational function in children. This mode of precision therapy should receive more attention and should be available to more patients with uncontrolled CHRNA4-related ADSHE across the age span. © 2020 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http:// creativecommons.org/licenses/by/4.0/).

We aimed to assess stereoelectroencephalography (SEEG) seizure-onset and interictal patterns associated with MRI-negative epilepsy and investigate their possible links with histology, extent of the epileptogenic zone (EZ) and surgical outcome. We retrospectively analysed a cohort of 59 consecutive MRI-negative surgical candidates, who underwent SEEG recordings followed by cortectomy between 2000 and 2016. Most of the eight distinct seizure-onset patterns could be encountered both in confirmed focal cortical dysplasia (FCD) and in histologically non-specific or normal cases. We found strong correlation (p = 0.008) between seizure-onset pattern and histology for: (1) slow-wave/DC-shift prior to low voltage fast activity (LVFA), associated with normal/non-specific histology, and (2) bursts of polyspikes prior to LVFA, exclusively observed in FCD. Three interictal patterns were identified: periodic slow-wave/gamma burst, sub-continuous rhythmic spiking and irregular spikes. Both “periodic” patterns were more frequent in but not specific to FCD. Surgical outcome depended on the EZ complete removal, regardless electrophysiological features. Histologically normal and FCD-associated epileptogenic zones share distinct interictal and ictal electrophysiological phenotypes, with common patterns between FCD subtypes and between dysplastic and apparently normal brain. Some specific seizure-onset patterns seem to be predictive of the underlying histology and may help to detect an MRI-invisible FCD.

Structural epilepsy related to cerebral arteriovenous malformation (AVM) suggests different epileptogenic mechanisms. The aim of our study was to determine factors associated with epilepsy into a retrospective cohort of AVM patients.Ruptured and unruptured AVM data retrieved from a prospective single center registry (2009-2016) were retrospectively assessed. Demographic, clinical and radiological features were identified in AVM patients with or without epilepsy according to the International League Against Epilepsy classification.Epilepsy concerned 22 out of 80 consecutive patients with AVM (27.5%). Univariate analysis comparing both groups revealed a significant association of different variables with the structural epilepsy: young age (P=0.02), large nidus size (P=0.02), venous dilation (P=0.02), posterior cerebral artery (PCA) feeder (P0.001) and Spetzler-Martin grade (P=0.02). Based on multivariate analysis, only the PCA feeder was identified (OR=5.2 [95% CI 1.1-24,5], P=0.04).PCA feeder for cerebral AVM was significantly associated with structural epilepsy. The hypothesis of a vascular steal phenomenon to the detriment of internal temporal lobe vascularization could be related to the development of epilepsy.

Body awareness is the result of sensory integration in the posterior parietal cortex; however, other brain structures are part of this process. Our goal is to determine how the cingulate cortex is involved in the representation of our body. We retrospectively selected patients with drug‐resistant epilepsy, explored by stereo‐electroencephalography, that had the cingulate cortex sampled outside the epileptogenic zone. The clinical effects of high‐frequency electrical stimulation were reviewed and only those sites that elicited changes related to body perception were included. Connectivity of the cingulate cortex and other cortical structures was assessed using the h (2) coefficient, following a nonlinear regression analysis of the broadband EEG signal. Poststimulation changes in connectivity were compared between two sets of stimulations eliciting or not eliciting symptoms related to body awareness (interest and control groups). We included 17 stimulations from 12 patients that reported different types of body perception changes such as sensation of being pushed toward right/left/up, one limb becoming heavier/lighter, illusory sensation of movement, sensation of pressure, sensation of floating or detachment of one hemi‐body. High‐frequency stimulation in the cingulate cortex (1 anterior, 15 middle, 1 posterior part) elicits body perception changes, associated with a decreased connectivity of the dominant posterior insula and increased coupling between other structures, located particularly in the nondominant hemisphere.

Introduction The purpose of presurgical assessment is to delimit the epileptogenic zone and the functional deficit zone with a brain MRI, an electroencephalograph or even a stereo-electroencephalograph (SEEG), neuropsychological evaluation, and a cerebral FDG PET. Several studies concur that the hypometabolism of FDG PET seems to be consistent with epileptogenic zones. We compared the functional deficit zone defined by FDG PET with the results of the SEEG, for each cluster electrode contact (CEC) located in the gray matter. Methods The electrode diagram of the 15 patients (486 CECs) operated on for drug-resistant epilepsy was merged with MRI and FDG PET. The metabolisms of FDG PET and SEEG were compared using a logistic regression test. Results The presence of hypometabolism resulted in a significantly higher risk of being in the seizure onset zone and the irritative zone, particularly when it was intense. Of the deeply hypometabolic CECs, 47% were in the seizure onset zone and 76% in the irritative zone. Normal metabolism resulted in a significantly higher probability of being in the healthy zone. Conclusions This study demonstrated an association between the presence of normal metabolism and the location of CECs in the healthy zone, and between the presence of pathological metabolism and the location of CECs in the seizure onset zone and the irritative zone, with metabolism abnormalities progressively more present and more intense near the seizure onset zone.

Objective Epilepsy associated with periventricular nodular heterotopia (PNH) is characterized by complex relationships between the heterotopic and the normotopic cortex during the interictal state and at seizure onset. High-frequency oscillations (HFO) have been proposed as a marker of epileptogenicity that might reflect disease activity. The effects of thermocoagulations on epileptogenicity in this context remain unknown. We aimed to investigate the interictal HFO- and spike profiles of different cortical structures before and after two consecutive SEEG-guided thermocoagulations, in correlation with seizure outcome, in a patient with PNH-related drug-resistant epilepsy. Methods The epileptogenic zone (EZ) was defined by SEEG analysis based on the Epileptogenicity Index. Interictal spikes, ripples (80–250 Hz) and fast ripples (FR, 250-330 Hz) were analyzed within the heterotopia, the temporal neocortex and the hippocampus. Results The SEEG recordings revealed a distributed EZ involving the heterotopia and the posterior temporal neocortex. Both structures were targeted by thermocoagulations. Background spikes, ripples and FR-rates were significantly higher in PNH compared to the normotopic cortex. A drastic reduction of spikes (by over 80%) and absence of FR were demonstrated both in the PNH and in the neocortex during the second SEEG exploration 6 months after the first thermocoagulation, whereas no significant difference was observed in the posterior hippocampus. Ripples were significantly reduced by the first and suppressed by the second thermocoagulation within the three structures. Seizures relapsed after two months but decreased in frequency after the first thermocoagulation. Sustained seizure-freedom was achieved only after the second procedure. Conclusions Our data demonstrate the running down of interictal HFO and spikes within the epileptogenic network following thermocoagulations of heterotopic and normotopic sites involved at seizure onset. This dynamics was in good correlation with significantly improved seizure control. Significance Combination of ictal and different interictal markers of epileptogenicity, including HFO and spike analysis, is important to get the full picture of the epileptogenic zone and could help to evaluate the disease activity.

L’epilepsie est une pathologie tres repandue, avec une prevalence de 600 000 personnes en France, ce qui correspond a 1 % de la population, dont la moitie sont des adultes. Dans 30 % des cas, la reponse au traitement medicamenteux est insatisfaisante, avec persistance de crises. Bien que les manifestations cliniques de cette maladie soient diverses, celles-ci sont frequemment associees a des difficultes d’insertion en milieu scolaire ou professionnel ordinaire. On releve ainsi un taux de chomage des patients epileptiques jusqu’a 2 fois plus eleve que celui de la population generale. Devant la necessite d’une double expertise concernant la pathologie epileptique et la connaissance du milieu professionnel, les hopitaux universitaires de Strasbourg ont mis en place en novembre 2016 une reunion de concertation pluridisciplinaire (RCP) centree sur la problematique de l’epilepsie et du travail. Celle-ci reunit une fois par trimestre au moins un medecin du travail du service de pathologie professionnelle, un neurologue ainsi qu’une assistance sociale de l’unite d’epileptologie. La voie d’entree des patients beneficiant de cette RCP peut se faire via le service de neurologie dans un objectif d’insertion en milieu professionnel, ou via le service de pathologie professionnelle en cas de problematique relative a la compatibilite entre le poste occupe et les manifestations cliniques de la pathologie. Les objectifs en sont d’evaluer le contexte medico-socioprofessionnel, d’informer le patient sur ses droits et les dispositifs d’insertion disponibles, l’accompagner dans ses demarches et enfin de faire le lien avec les differents intervenants (neurologue, medecin traitant, assistant social, medecin du travail, structures d’aide au maintien dans l’emploi…). Apres une annee de fonctionnement, les dossiers de 16 patients ont ete abordes. Pres de la moitie de ces patients etaient sans activite professionnelle. L’autre moitie exercait des metiers ne necessitant que peu de qualifications et sur des contrats de travail precaires (interimaires). L’orientation a ete discutee au cas par cas, avec des preconisations pour des amenagements de poste, orientations conseillees vers un poste en milieu adapte ou protege, voire des conseils et appuis dans le cadre d’un dossier de demande d’invalidite, 1re ou 2e categorie. La mise en place de cette RCP a permis de repondre a des problematiques specifiques et recurrentes au sein de l’unite « malaise et epilepsie » et de pathologie professionnelle, d’ameliorer la prise en charge des patients, mais aussi de mutualiser la responsabilite des decisions pour le medecin du travail, qui ne dispose pas toujours de toutes les informations necessaires pour etablir un pronostic de la pathologie.

Summary Purpose: The continuous spike and waves during slow-wave sleep syndrome (CSWSS) and the Landau-Kleffner (LKS) syndrome are two rare epileptic encephalopathies sharing common clinical features including seizures and regression. Both CSWSS and LKS can be associated with the electroencephalography pattern of electrical status epilepticus during slow-wave sleep and are part of a clinical continuum that at its benign end also includes rolandic epilepsy (RE) with centrotemporal spikes. The CSWSS and LKS patients can also have behavioral manifestations that overlap the spectrum of autism disorders (ASD). An impairment of brain development and/or maturation with complex interplay between genetic predisposition and nongenetic factors has been suspected. A role for autoimmunity has been proposed but the pathophysiology of CSWSS and of LKS remains uncharacterized. Methods: In recent years, the participation of rare genomic alterations in the susceptibility to epileptic and autistic disorders has been demonstrated. The involvement of copy number variations (CNVs) in 61 CSWSS and LKS patients was questioned using comparative genomic hybridization assays coupled with validation by quantitative polymerase chain reaction (PCR). Key Findings: Whereas the patients showed highly heterogeneous in genomic architecture, several potentially pathogenic alterations were detected. A large number of these corresponded to genomic regions or genes (ATP13A4, CDH9, CDH13, CNTNAP2, CTNNA3, DIAPH3, GRIN2A, MDGA2, SHANK3) that have been either associated with ASD for most of them, or involved in speech or language impairment, or in RE. Particularly, CNVs encoding cell adhesion proteins (cadherins, protocadherins, contactins, catenins) were detected with high frequency (≈20% of the patients) and significant enrichment (cell adhesion: p = 0.027; cell adhesion molecule binding: p = 9.27 × 10−7). Significance: Overall our data bring the first insights into the possible molecular pathophysiology of CSWSS and LKS. The overrepresentation of cell adhesion genes and the strong overlap with the genetic, genomic and molecular ASD networks, provide an exciting and unifying view on the clinical links among CSWSS, LKS, and ASD.

Auteur(s) : MP Valenti, B Cretin, C Davanture, S Dylgjeri, C Boulay, C Zaencker, P Kehrli, E Hirsch1 1Pole Tete-Cou-CETD, 1 place de l’hopital 67091 Strasbourg France; 1 CTRS-IDEE, Lyon B. Lisa est une adolescente de 18 ans, droitiere, nee le 21 octobre 1990, actuellement en terminale ES et sans antecedent personnel ou familial. A l’âge de 12 ans, cette jeune fille rapporte l’installation, en quelques semaines, de cephalees, suivies par une baisse de l’acuite visuelle [...]

Genetic generalized epilepsy (GGE), formerly known as idiopathic generalized epilepsy, is the most common form of epilepsy and is thought to have predominant genetic etiology. GGE are clinically characterized by absence, myoclonic, or generalized tonic-clonic seizures with electroencephalographic pattern of bilateral, synchronous, and symmetrical spike-and-wave discharges. Despite their strong heritability, the genetic basis of generalized epilepsies remains largely elusive. Nevertheless, recent advances in genetic technology have led to the identification of numerous genes and genomic defects in various types of epilepsies in the past few years. In the present study, we performed whole-exome sequencing in a family with GGE consistent with the diagnosis of eyelid myoclonia with absences. We found a nonsense variant (c.196C>T/p.(Arg66*)) in RORB, which encodes the beta retinoid-related orphan nuclear receptor (RORβ), in four affected family members. In addition, two de novo variants (c.218T>C/p.(Leu73Pro); c.1249_1251delACG/p.(Thr417del)) were identified in sporadic patients by trio-based exome sequencing. We also found two de novo deletions in patients with behavioral and cognitive impairment and epilepsy: a 52-kb microdeletion involving exons 5-10 of RORB and a larger 9q21-microdeletion. Furthermore, we identified a patient with intellectual disability and a balanced translocation where one breakpoint truncates RORB and refined the phenotype of a recently reported patient with RORB deletion. Our data support the role of RORB gene variants/CNVs in neurodevelopmental disorders including epilepsy, and especially in generalized epilepsies with predominant absence seizures.European Journal of Human Genetics advance online publication, 29 June 2016; doi:10.1038/ejhg.2016.80.

In a 1992 editorial article, Landau expressed the hope of collective agreement in the medical community about Landau-Kleffner syndrome (LKS) in terms of diagnosis criteria, etiology, pathophysiology and rational therapy. Since then, neurophysiological and neuroimaging studies have led to the view that LKS is an acquired aphasia, secondary to an epileptic disturbance affecting a cortical area involved in verbal processing. This fits with the hypothesis of a "functional ablation" caused by epileptic activity. Under these criteria, epileptic aphasia becomes a subgroup of the continuous spike-waves syndrome in which epileptic discharges originate from the temporal cortex. Genetic predisposition for KLS could be related to hyperexcitability and synchronization of interneurons within the perisylvian cortices, which generate the spike-waves. Activation of these waves during NREM sleep, following thalamo-cortical uncoupling, might then alter the blood brain barrier and provoke an autoimmune reaction. Interneuron hyperactivity might in turn have an antiepileptic protective effect, associated with the inhibition of a specific function, and spike-waves activity over the long term might eventuate in focal atrophy. This morphological defect might explain the poor verbal outcome in some cases of LKS. From this study we recommend a multicenter control study of good design and methodology be carried out to compare the efficacies of early versus delayed (3 months) corticosteroid treatment in patients with typical LKS that is being treated by clobazam (or diazepam) monotherapy.

Summary: Purpose: Language-induced epilepsy involves seizure precipitation by speaking, reading, and writing. Seizures are similar to those of reading epilepsy (RE). The nosologic position of language-induced epilepsy is not clear. We performed a clinical and neurophysiological study in a multigenerational family with the association of idiopathic generalized epilepsy (IGE) with ictal stuttering as a manifestation of reflex language-induced epilepsy. Methods: Nine members on three generations were studied. All patients underwent video-polygraphic EEG recordings (awake and during sleep). A standardized protocol was applied to test the effect of language and non–language-related tasks. Results: Six patients presented language-induced jaw jerking that mimicked stuttering and corresponded to focal myoclonus involving facial muscles. This was associated with an IGE phenotype in four of these patients. Focal EEG spikes were found in all six patients by visual analysis and/or back-averaging techniques. The focal spikes were either asymptomatic (when followed by a slow wave) or symptomatic of facial myoclonia (when isolated). Levetiracetam, used as add-on or monotherapy in four patients, suppressed ictal stuttering. One additional case only had a phenotype of IGE without focal features. Conclusions: This family study demonstrates the phenotypic heterogeneity of the association of IGE phenotype with ictal stuttering (language-related reflex seizure). Our data suggest that this particular form of reflex epilepsy related to language has more similarities with generalized epilepsies than with focal ones. Neurophysiological investigations should be performed more systematically in patients with acquired stuttering, especially if there is family history of IGE.

Introduction Le syndrome FIRES correspond a une encephalopathie epileptique survenant chez l’enfant. Nous rapportons les observations de deux femmes adultes ayant presentees un tableau clinique proche a celui decrit chez l’enfant. Observation Deux patientes âgees de 29, 30 ans ont developpe une « epilepsie focale symptomatique » a crises temporo-peri-sylviennes uni- ou bilaterales pharmacoresistantes faisant suite a un episode infectieux et un etat de mal epileptique. Les bilans infectieux et immunitaires pousses n’ont pas permis de trouver de causes. Les traitements par immunoglobulines se sont averes inefficaces. Par contre, une approche chirurgicale dans un cas et un regime cetogene dans l’autre cas ont permis une amelioration de la situation avec une disparition des crises chez la patiente operee. Les donnees neuropathologique seront rapportees. Discussion Ces deux observations laissent a penser que le syndrome FIRES n’existe pas uniquement chez l’enfant de 3 a 17 ans. Dans le cadre des « epilepsies focales symptomatiques », le syndrome FIRES, doit-il etre distingue : des epilepsies post-infectieuses ou post-encephalites, des encephalites limbiques, du syndrome hemiplegie hemi-convulsion epilepsie (HHE) et de l’epilepsie temporo-mesiale avec sclerose de l’hippocampe. Conclusion Le syndrome FIRES chez l’adulte doit-il etre individualise ? Il depend probablement de plusieurs facteurs etiologiques (genetique–infectieux–immunitaire). Il n’est pas une contre-indication a la realisation d’un traitement chirurgical. Informations complementaires Absence de financements particuliers, publics ou prives.

Introduction La stereo-electroencephalographie (SEEG) est une methode d’exploration invasive de l’epilepsie focale pharmacoresistante ayant pour buts d’identifier la zone epileptogene (ZE) et d’evaluer des possibilites de resection chirurgicale. Objectifs Nous avions pour objectif d’etudier le benefice therapeutique de la SEEG sur le controle de crises chez les patients epileptiques dont le projet chirurgical n’a pas abouti a l’issue de l’exploration invasive. Patients et methodes Parmi les 114 explorations SEEG pour une epilepsie focale pharmacoresistante realisees dans notre centre entre 2004 et 2015, 22 patients n’ayant pas subi une cortectomie ont ete retrospectivement identifies. Dix-huit cas etaient inclus selon les criteres suivants : crises epileptiques confirmees en SEEG ; pas de thermocoagulations. L’evolution post-SEEG en termes de frequence des crises a ete analysee et comparee aux donnees epidemiologiques, a l’imagerie, a la topographie de la ZE, et au nombre d’electrodes implantees. Resultats Une amelioration significative et durable apres la SEEG a ete observee chez 6 patients sur 18 (33 %), avec l’absence complete de crises pendant min. Un an chez 4 et diminution de la frequence de crises > 90 % chez 2 (duree de suivi 1–8 ans). L’etiologie etait structurelle (DNET ou gangliogliome, n = 3) ou inconnue ( n = 3). Il n’a pas ete trouve de correlation entre le bon controle de crises apres la SEEG et les facteurs epidemiologiques, etiologiques ou electrophysiologiques analyses. Discussion Nos donnees suggerent la possibilite d’un effet therapeutique non negligeable de la SEEG en termes de diminution de la frequence des crises dans l’epilepsie focale pharmacoresistante. Ces resultats sont comparables a l’efficacite decrite pour les thermocoagulations (Cossu et al., 2015). Une modification du reseau epileptogene due a des multiples microlesions sequellaires reste une hypothese physiopathologique attractive. Conclusion Outre sa valeur diagnostique, la SEEG offre une option therapeutique qui ne constitue pas une alternative a la chirurgie de resection mais peut s’averer benefique lorsque l’on conclut a une non-operabilite.

Objectives We aim to map the function and connectivity of the cingulate gyrus (CG) using cortical direct electrical stimulation. Methods We selected patients explored by SEEG at the Emergency University Hospital Bucharest and at the Strasbourg University Hospital, that had minimum one electrode sampling the CG (anterior-ACG, middle-MCG or posterior-PCG), outside the epileptogenic zone. We systematically reviewed the functional stimulations (bipolar, 50 Hz, 0.25–3 mA). For 17 patients explored in Bucharest, cortico-cortical evoked potentials (CCEPs) elicited by single pulse electrical stimulations (SPES) were used to obtain the effective connectivity at a group level for each part of the CG. Results We included 429 bipolar stimulations from 108 patients. From 151 stimulations in the ACG, 24.5% elicited a clinical response like: emotions (19%), vestibular (13.5%), thoracic sensation (13.5%), smile (11%). There are 135 stimulations in the MCG of which 53.3% elicited clinical responses like: elementary motor (24.94%), proprioception (22.22%), elementary somatosensitive (13.2%), compulsive motor (2.77%). There were 143 stimulations in the PCG and only 18.88% were positive, for example: executive function (11.11%), vestibular (7.4%). CCEPs analysis revealed that ACG is connected with the prefrontal (frontobasal and frontopolar) regions, anterior insula, mesiotemporal regions. MCG is connected with the primary and supplementary motor areas, insulo-perisylvian region and parietal lobe. PCG is connected with the ACG, MCG, prefrontal, parietal and temporal regions. Discussion High frequency stimulations elicit clinical responses as a result of a network effect that we have mapped with CCEPs. Conclusions There is a regional organization of the cingulate gyrus for each part both in function and connectivity. Significance These findings help us understand the functional organization of the cingulate gyrus with possible implications in epilepsy surgery, depression or other mental disorders.

Epileptic encephalopathy with continuous diffuse spike-waves during slow-wave sleep (ECSWS) presents clinically with infrequent nocturnal focal seizures, atypical absences related to secondary bilateral synchrony, negative myoclonia, and atonic and rare generalized tonic-clonic seizures. The unique electroencephalography (EEG) pattern found in ECSWS consists of continuous, diffuse, bilateral spike-waves during slow-wave sleep. Despite the eventual disappearance of clinical seizures and EEG abnormalities by adolescence, the prognosis is guarded in most cases because of neuropsychological and behavioral deficits. ECSWS has a heterogeneous etiology (genetic, structural, and unknown). Because epilepsy and electroencephalography (EEG) abnormalities in epileptic encephalopathy with continuous diffuse spike-waves during slow-wave sleep (ECSWS) are self-limited and age related, the need for ongoing medical care and transition to adult care might be questioned. For adolescents in whom etiology remains unknown (possibly genetic) and who experience the disappearance of seizures and EEG abnormalities, there is rarely need for long-term neurologic follow-up, because often a relatively normal cognitive and social evolution follows. However, the majority of patients with structural and possibly "genetic syndromic" etiologies will have persistent cognitive deficits and will need suitable socioeducative care. Therefore, the transition process in ECSWS will depend mainly on etiology and its related features (epileptic active phase duration, and cognitive and behavioral evolution) and revolve around neuropsychological and social support rather than medical and pharmacologic follow-up.

Introduction Le stroke like migraine after radiation therapy (SMART) syndrome associe cephalees, troubles neurologiques aigus, crises epileptiques et prise de contraste corticale a l’IRM, a distance d’une radiotherapie cerebrale. Observation Un patient droitier de 42 ans (no 1974278), aux antecedents de migraines et de lesion gliale parietale droite non etiquetee a ete traitee en 2002 par radiotherapie et chimiotherapie adjuvante dans l’hypothese d’une lesion de haut grade. Dix ans plus tard, le patient developpe une epilepsie focale pharmacoresistante d’origine structurelle suspectee mais avec des atypies motivant une exploration invasive par video-stereo-electro-encephalographie (SEEG) dans une demarche pre-chirurgicale. Quarante-huit heures apres l’implantation des electrodes profondes, le patient presente des cephalees, un deficit sensitivo-moteur du membre superieur gauche, une heminegligence, un ralentissement psycho-moteur et des crises focales a semiologie electro-clinique inhabituelle. Les electrodes sont explantees en urgence et une IRM cerebrale est realisee qui montre un oedeme cortical massif et une prise de contraste corticale des regions centro-parietales, temporales et insulaires droites, avec augmentation du coefficient apparent de diffusion. Dans l’hypothese d’un SMART syndrome et devant la persistance de crises refractaires au traitement anticonvulsif, une corticotherapie intraveineuse a fortes doses a ete mise en place avec une regression complete du tableau clinico-radiographique en 72 h. Discussion Le SMART syndrome est une complication rare, retardee et presque toujours reversible, de la radiotherapie des tumeurs cerebrales. Les hypotheses physiopathologiques sont (i) une vasculopathie reversible ou (ii) une atteinte neuronale avec alteration du systeme trigemino-vasculaire ou baisse du seuil pour la depression corticale envahissante. Le plus souvent spontane, un SMART syndrome peut rarement etre induit par une chirurgie tumorale. Conclusion A notre connaissance, le SMART syndrome survenant lors d’une exploration SEEG n’a jamais ete decrit. Le rapport benefice-risque doit etre pris en compte avant un geste neurochirurgical en cas d’antecedent de radiotherapie.

Niemann-Pick type C disease (NPC) is a recessive neurolipidosis. We report five adolescent and adult NPC cases to underscore the frequency and heterogeneity of movement disorders in NPC. Clinical, morphologic, biochemical and genetic study was performed in the five patients. Disease onset was between 8 and 50 years. Movement disorders were present in all cases, were heterogeneous and often combined [cerebellar ataxia (5/5), myoclonus (3/5), dystonia (2/5), chorea (1/5) and tremor (1/5)] and were the first sign in 4/5. Two patients were reported to have no vertical supranuclear gaze palsy (VSGP) at the first examination. Two patients experienced acute neuropsychiatric signs leading to death in one case due to myoclonic storm. Filipin staining was always positive. Two NPC1 mutations were identified in three patients, only one in two siblings. NPC should be considered in case of unexplained movement disorders, even when VSGP or cataplexy are not reported. Filipin staining remains a strong support for the diagnosis. Treatment with miglustat should be considered which is currently the only approved disease-specific treatment of NPC in children and adults.

Epilepsy is a common disorder but diagnosis remains largely clinical. Although MRI and EEG significantly aid the diagnosis of epilepsy, these techniques may also be misleading and indicate abnormalities not related to phenomenology. Consequences of erroneous diagnosis of epilepsy may lead to aggressive and escalating pharmacotherapy with potentially serious side effects. Metabolic disorders, which may mimic epilepsy, should always be considered as they are potentially curable and may be fatal if untreated. We report a case of an insulinoma, misdiagnosed as temporal lobe epilepsy. We highlight the risks associated with misinterpretation of neuroimaging and EEG and outline an approach to differentiate between symptoms of insulinoma or neuroglycopenia and temporal epileptic seizures.

Epilepsy is a frequent neurologic disease in childhood, characterized by recurrent seizures and sometimes with major effects on social, behavioral, and cognitive development. Childhood focal epilepsies particularly are age-related diseases mainly occurring during developmental critical periods. A complex interplay between brain development and maturation processes and susceptibility genes may contribute to the development of various childhood epileptic syndromes associated with language and cognitive deficits. Indeed, the Landau-Kleffner syndrome (LKS), the continuous spike-and-waves during sleep syndrome (CSWS), and the benign childhood epilepsy with centrotemporal spikes (BCECTS) or benign rolandic epilepsy, are different entities that are considered as part of a single continuous spectrum of disorders. Genetic predisposition with simple to complex modes of inheritance has long been suspected for this wide group of childhood focal epilepsies. Recent reports on the involvement of the SRPX2 and ELP4 genes with possible roles in cell motility, migration, and adhesion have provided first insights into the complex molecular bases of childhood focal epilepsies.

Summary Purpose: This retrospective study aims to review the electroclinical features of patients presenting with eyelid myoclonia (EM) with and without absences. Methods: The Italian chapter of the International League Against Epilepsy (ILAE) has been conducting an electroclinical study of patients with EM. Among these, we searched for and selected the patients presenting with both impairment of intellectual functions and a peculiar ictal electroencephalography (EEG) pattern, that is, a discharge of fast generalized polyspikes/polyspikes and waves. Results: We found 18 patients matching this electroclinical picture. All the patients were photosensitive. All of them had associated generalized, mostly nocturnal, tonic–clonic seizures. During the evolution, 13 patients presented episodes of EM status. Despite adequate antiepileptic treatment, the patients remained drug resistant for many years or throughout the evolution. The degree of impairment of intellectual functions varied from borderline level to moderate mental retardation. Discussion: The patients we described herein can be considered a homogeneous group in the more heterogeneous group of patients presenting with EM. Further clinical and, more probably, genetic studies will clarify whether this condition could be considered a specific and homogeneous condition in the more heterogeneous group of patients presenting with EM.

The rolandic and sylvian fissures divide the human cerebral hemispheres and the adjacent areas participate in speech processing. The relationship of rolandic (sylvian) seizure disorders with speech and cognitive impairments is well known, albeit poorly understood. We have identified the Xq22 gene SRPX2 as being responsible for rolandic seizures (RSs) associated with oral and speech dyspraxia and mental retardation (MR). SRPX2 is a secreted sushi-repeat containing protein expressed in neurons of the human adult brain, including the rolandic area. The disease-causing mutation (N327S) resulted in gain-of-glycosylation of the secreted mutant protein. A second mutation (Y72S) was identified within the first sushi domain of SRPX2 in a male with RSs and bilateral perisylvian polymicrogyria and his female relatives with mild MR or unaffected carrier status. In cultured cells, both mutations were associated with altered patterns of intracellular processing, suggesting protein misfolding. In the murine brain, Srpx2 protein expression appeared in neurons at birth. The involvement of SRPX2 in these disorders suggests an important role for SRPX2 in the perisylvian region critical for language and cognitive development.

Single photon emission computed tomography (SPECT) is currently used in the presurgical evaluation of medically intractable partial epilepsies, but not very often, in generalized epilepsy. In the present study, we used the SISCOM procedure, which represents the fusion of MRI and ictal-interictal difference SPECT images using (99m)Tc-ECD, to study cerebral blood flow changes during the ictal and postictal phases of typical childhood absence seizures. The study was performed on four children with typical, difficult to treat absence seizures, aged 10-13 years at the time of scan. The delay between the onset of absence seizures and the injection of (99m)Tc-ECD was carefully noted. One scan was performed during the ictal phase and showed diffuse blood flow decreases, while the three other scans performed during the postictal phase, showed generalized blood flow increase. These data are consistent with most previous data reporting generalized changes in functional activity, not limited to the thalamo-cortical circuit in which absence seizures originate, and a decrease in cerebral blood flow during the ictal phase. Our data are concordant with the hypothesis that neuronal activity underlying the occurrence of spike-and-wave discharges does not seem to require an increase in metabolic demand and blood flow rates. [Published with videosequences].

Paroxysmal motor phenomena and arousals during sleep are frequent. The differential diagnoses between benign hypnic transient events, epileptic and non-epileptic seizures represent a common clinical problem. Video-EEG monitoring during sleep, recording several episodes in the same patient, is essential in order to characterize these phenomena. It offers the possibility to compare electro-clinical data, to demonstrate the eventual stereotyped pattern of motor phenomena and their progression in time, and to study EEG-polygraphic correlates. The recently described double split-screen synchronized display (DSSSD) technique represents a useful tool for comparing particular clinical patterns of epileptic seizures when dealing with complex, hypermotor phenomena observed in frontal lobe epilepsy. We reviewed the data of 24 patients admitted during a two-year period (2002-2003) to our epilepsy sleep unit for isolated paroxysmal sleep motor events. Four patients presented with very brief paroxysmal arousals without daytime fits. Three of our patients presented isolated paroxysmal arousals, whereas in one, the events were associated with hypermotor seizures. We present a simplified variant of the DSSSD method (modified DSSSD) that can be used to study episodes of paroxysmal arousals in order to confirm their stereotyped motor pattern. The clinical aspects and the EEG-polygraphy patterns were informative, with the absence of asymmetrical tonic or dystonic posturing of the limbs. Scalp EEG alone does not usually provide much information in patients with isolated paroxysmal arousals. Coupled to the modified DSSSD technique, it may allow confirmation of the diagnosis of frontal epilepsy, as was the case in our four patients. [Published with video sequences].