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To study long-term clinical and cognitive outcomes of patients with anti-N-methyl-d-aspartate receptor encephalitis (NMDAR-E), an acute autoimmune neurological disease with severe acute presentations.In this French multicentre retrospective observational cohort study, patients no older than 18 years with a follow-up of at least 2 years were included. Data from clinical and cognitive assessments were collected.Eighty-one patients were included (57 females, 24 males; median age 10 years 7 months [range 1-18 years], median follow-up 40 months [range 25-53 months]). At last follow-up, 35 patients (45%) had cognitive impairment, 48 (70%) had academic difficulties, and 65 (92%) needed rehabilitation. Seventy-one patients (88%) had a modified Rankin Scale score of no more than 2. A higher number of symptoms at diagnosis was associated with cognitive impairment (p = 0.01), while an abnormal electroencephalogram at diagnosis increased the risk of academic difficulties (p = 0.03).Although most children with NMDAR-E seemed to recover from motor disabilities, more than 45% had cognitive and academic difficulties. The initial severity of symptoms seems to have an impact on cognition and academic performances.

γ-Aminobutyric acid (GABA)We collected clinical, electrophysiological, therapeutic, and molecular data from patients with GABAWe gathered the reported patients in three epileptic phenotypes: 15 patients with fever-related epilepsy (40%), 11 with early developmental epileptic encephalopathy (30%), 10 with generalized epilepsy spectrum (27%), and 1 patient without seizures (3%). We did not find a specific phenotype for any gene, but we showed that the location of variants on the transmembrane (TM) segment was associated with a more severe phenotype, irrespective of the GABAGABA

Objective Asparagine‐linked glycosylation 13 (ALG13) deficiencies have been repeatedly described in the literature with the clinical phenotype of a developmental and epileptic encephalopathy (DEE). Most cases were females carrying the recurrent ALG13 de novo variant, p.(Asn107Ser), with normal transferrin electrophoresis. Methods We delineate the phenotypic spectrum of 38 individuals, 37 girls and one boy, 16 of them novel and 22 published, with the most common pathogenic ALG13 variant p.(Asn107Ser) and additionally report the phenotype of three individuals carrying other likely pathogenic ALG13 variants. Results The phenotypic spectrum often comprised pharmacoresistant epilepsy with epileptic spasms, mostly with onset within the first 6 months of life and with spasm persistence in one‐half of the cases. Tonic seizures were the most prevalent additional seizure type. Electroencephalography showed hypsarrhythmia and at a later stage of the disease in one‐third of all cases paroxysms of fast activity with electrodecrement. ALG13‐related DEE was usually associated with severe to profound developmental delay; ambulation was acquired by one‐third of the cases, whereas purposeful hand use was sparse or completely absent. Hand stereotypies and dyskinetic movements including dystonia or choreoathetosis were relatively frequent. Verbal communication skills were absent or poor, and eye contact and pursuit were often impaired. Significance X‐linked ALG13‐related DEE usually manifests as West syndrome with severe to profound developmental delay. It is predominantly caused by the recurrent de novo missense variant p.(Asn107Ser). Comprehensive functional studies will be able to prove or disprove an association with congenital disorder of glycosylation.

Autoscopic phenomena (AP) are characterized by seeing an image of oneself in extra-personal space. These phenomena are rare and the anatomy of brain regions producing these phenomena is not well defined. We report anatomical electroclinical correlations during a stereoelectroencephalography-recorded seizure with autoscopic hallucination (a form of AP in which the double of oneself is seen from an internal point of view). Seizure onset zone was quantified using the epileptogenicity index method (EI). Maximal EI values were obtained in the left lateral parietal cortex (supramarginal gyrus) and high values were also found in the left posterior-superior insular cortex, left temporo-occipital junction and contralateral inferior parietal lobule. Our case confirms the involvement of the inferior parietal lobule, temporo-parieto-occipital junction and posterior insula in the genesis of autoscopic hallucination.

Purpose. Several weeks after COVID-19 infection, some children report the persistence or recurrence of functional complaints. This clinical presentation has been referred as “long COVID” in the adult population, and an 18F-FDG brain PET hypometabolic pattern has recently been suggested as a biomarker. Herein, we present a retrospective analysis of 7 paediatric patients with suspected long COVID who were explored by 18F-FDG brain PET exam. Metabolic brain findings were confronted to those obtained in adult patients with long COVID, in comparison to their respective age-matched control groups. Methods. Review of clinical examination, and whole-brain voxel-based analysis of 18F-FDG PET metabolism of the 7 children in comparison to 20 paediatric controls, 35 adult patients with long COVID and 44 healthy adult subjects. Results. Paediatric patients demonstrated a similair brain hypometabolic pattern as that found in adult long COVID patients, involving bilateral medial temporal lobes, brainstem and cerebellum (p-voxel < 0.001, p-cluster < 0.05 FWE-corrected), and also the right olfactory gyrus after small volume correction (p-voxel = 0.010 FWE-corrected), with partial recovery in two children at follow-up. Conclusion. These results provide arguments in favour of possible long COVID in children, with a similar functional brain involvement to those found in adults.

International audience; Objective: This longitudinal study aimed to measure the time course of intellectual changes after pediatric focal resective epilepsy surgery and to identify their predictors.Methods: We analyzed a cohort of 81 school-aged children with focal epilepsy and intractable seizures who underwent neurosurgery (focal resection) from 2000 to 2018 in La Timone Hospital (Marseille). Neuropsychological assessments were carried out before and then 1, 2, 3, and 5 years after epilepsy surgery.Results: Eighty-one patients with a median age at surgery of 13.74 years [4.25] were enrolled. Overall, 45 of the 81 (55%) recruited patients were improved after the surgery on at least one of the five domains of the Wechsler Intelligence Scale. Temporal lobe localization and postoperative seizure freedom were the main prognostic factors impacting intellectual outcome (improvement and decline) after epilepsy surgery. Younger patients at surgery were less likely to have a postoperative IQ decline. Intellectual improvement after epilepsy surgery could be delayed for up to 5 years after surgery and concerned all intellectual domains except the Verbal Comprehension Index (VCI). Intellectual decline after epilepsy surgery occurred mainly during the first two years after the surgery and was reflected in full-scale intelligence quotient (FSIQ) and Working Memory Index (WMI).Conclusions: Our study points out that children and adolescents with TLE who achieved freedom from seizure after epilepsy surgery are the leading candidates for achieving postoperative intellectual improvement. This enhancement in intellectual function shows a long time course, whereas intellectual decline is evidenced earlier.

Objective: To assess adverse events (AEs) and efficacy of add-on cannabidiol (CBD) with a slower titration protocol in pediatric clinical practice. Methods: We conducted a prospective, open-label, multicenter study in seven French reference centers for rare epilepsies. Patients had slow titration to reach a target dose of 10 mg/kg/day within at least 1 month and then gradually increased to a maximum dose of 20 mg/kg/day. We analyzed AEs and efficacy at M1 (month 1), M2, and M6, comparing two sets of subgroups: Dravet syndrome (DS) vs. Lennox-Gastaut (LGS) and patients with clobazam (CLB+) vs. patients without (CLB−). Results: One hundred and twenty-five patients were enrolled (62 LGS, 48 DS, 5 Tuberous sclerosis, and 10 other etiologies). Median concomitant antiepileptic drugs (AEDs) was three (25th percentile: 3, 75th percentile: 4). Patients received a dose of 10 (10–12), 14 (10–20), and 15.5 mg/kg/day (10–20) at M1, M2, and M6, respectively. Twenty-six patients discontinued CBD, 19 due to lack of efficacy, 2 due to AEs, 4 for both, and 1 had a sudden unexpected death in epilepsy. AEs were reported in 61 patients (48.8%), mainly somnolence (n = 26), asthenia (n = 20), and behavior disorders (n = 16). Abnormal transaminases (≥3 times) were reported in 11 patients receiving both valproate and clobazam. AEs were significantly higher at M2 (p = 0.03) and increased with the number of AEDs (p = 0.03). At M6, total seizure frequency change from baseline was −41% ± 37.5% (mean ± standard deviation), and 28 patients (37.8%) had a reduction ≥50%. AE and efficacy did not differ between DS vs. LGS and CLB+ vs. CLB– patients. Significance: A slower titration of CBD dose delivered better tolerance with comparable efficacy to previous trials. Concomitant CLB did not increase efficacy rates but in a few cases increased AEs. This slow titration scheme should help guide clinicians prescribing CBD and allow patients to benefit from its potential efficacy.

Purpose Ictal blinking may be observed in various forms of epilepsies. In the context of presurgical assessment of drug-resistant focal epilepsies, its semiological value is poorly understood. Our aims were to determine the prevalence and localizing value of ictal blinking. Methods We reviewed our cohort of more than 300 patients explored by SEEG, searching for ictal blinking. We defined seizure onset zone (SOZ) using visual analysis complemented by a quantified method (epileptogenicity index). We analysed the features of ictal blinking and the associated signs. We tested for statistically significant associations with the underlying SOZ. Results We found that about 8% of our patients exhibited ictal blinking, mostly bilateral. Ictal blinking was seen mostly in four types of SOZ: occipital, occipito-temporal, temporal mesial, and insulo-opercular. It was significantly over-represented in occipito-temporal and occipital SOZ. Eye blinking was fastest in insulo-opercular SOZ and slowest in temporal mesial SOZ. Nystagmus and tonic eye deviation were associated with SOZ involving the occipital lobe. Conclusion Ictal blinking is not uncommon in the population of patients with drug-resistant focal epilepsies. It is mostly associated with four types of SOZ: occipital, occipito-temporal, temporal mesial, and insulo-opercular. Some features of ictal blinking, as well as the analysis of the associated signs, allow to orient clinical hypotheses toward some specific SOZ.

OBJECTIVE Post-stroke epilepsy (PSE) represents a rare etiology in patients undergoing pre-surgical evaluation for epilepsy. Refractory PSE has been traditionally surgically treated with hemispherotomy. The aim of this study was to define the electrophysiological features of epileptogenic zone (EZ) using stereoelectroencephalography (SEEG) recordings in patients with refractory PSE. METHODS We analyzed ictal SEEG recordings from 21 consecutive patients. Epileptogenicity was quantified using the "epileptogenicity index" (EI) method in distant and perilesional cortical structures. We identified different seizure onset patterns (SOP) through a visual and time-frequency analysis. RESULTS We found that 81% of patients showed a complex organization of EZ, involving remote and perilesional structures. EZ involved a significantly (p 0.01) higher number of distant regions displaying a high epileptogenicity (EI ≥ 0.3). Low voltage fast activity (LFA) and high amplitude slow activity (HAS) patterns were observed respectively in 85.7% and 14.3% of patients. Surgery was proposed in 12/21 patients. Good surgical outcome (Engel Class I or II) was observed for all patients who underwent tailored functional disconnection based on SEEG results. Shorter epilepsy duration to surgery was found in the seizure-free group. SIGNIFICANCE Refractory PSE may present a complex organization of EZ. SEEG recordings are warranted to guide tailored hemispherectomy.

The objective of this study was to evaluate the Neurological Disorders Depression Inventory-Epilepsy (NDDI-E) for Youth (NDDI-E-Y) for screening for major depressive disorder (MDD) in French youth with epilepsy (YWE), in order to (1) validate this tool in a separate population; (2) determine whether the 12-item NDDI-E-Y affords advantages over the 6-item adult NDDI-E; (3) measure psychometric performance of each item.Youth with epilepsy aged 11-17 years completed a 15-item questionnaire to calculate total scores for NDDI-E-Y (12 items) and NDDI-E (6 items). Gold standard for MDD was Children's Depression Inventory (CDI). Receiver operator characteristic (ROC) analyses for total NDDI-E-Y and NDDI-E scores were compared. Psychometric properties of each item were analyzed for: floor/ceiling effect, item-internal consistency, and ROC curve.Ninety-seven YWE were included; 21.6% had MDD (CDI 15). Correlation was very high between total NDDI-E-Y and NDDI-E scores, and high between NDDI-E-Y and CDI. Cutoff point for the NDDI-E-Y maximizing both sensitivity and specificity was 23 (original study cutoff 32). The ROC analysis of the NDDI-E-Y showed an area under the curve (AUC) 0.967 (95% confidence intervals [CI] 0.909-0.992); (p 0.0001). Sensitivity, specificity, and positive (PPV) and negative predictive values (NPV) were 100% [83.9; 100], 82.9% [72.5; 90.6], 61.8 [43.6; 77.8], and 100% [94.3; 100], respectively. The NDDI-E-Y was not superior to NDDI-E according to pairwise comparison of ROC (p = 0.07). Psychometric analysis revealed marked differences between items. After eliminating items with poorer performance, a 6-item version of the NDDI-E-Y showed sensitivity, specificity, PPV, and NPV of 100% [85.5; 100], 85.5% [75.6; 92.5], 65.6 [46.8; 81.4], and 100% [94.5; 100], respectively. This was significantly better than the adult NDDI-E (p = 0.03) though not NDDI-E-Y (p = 0.07).Significant difference in cutoff indicates that the NDDI-E-Y cannot yet be recommended for widespread screening of MDD in YWE. Discrepancies in psychometric performance between items suggest that further work is needed to examine both validation of the original 12-item NDDI-E-Y and comparison with a shorter version.

Purpose In this study, we aimed to improve our knowledge of insular epilepsy by studying anatomoelectroclinical correlations in pure insular-onset epilepsy and characterizing differences between anterior and posterior insular-onset seizures. Methods Patients in whom seizure-onset zone was confined to the insula and peri-insular sulcus were selected from 301 consecutive presurgical stereo-electroencephalography (EEG) recordings performed between years 2010 and 2017 in two epilepsy centers. Ictal-onset zone in stereo-EEG was delineated visually and quantitatively using epileptogenic index method. Seizure characteristics were reanalyzed, and anatomoelectroclinical correlations were assessed. Characteristics of posterior and anterior insular-onset seizures were compared. Results Eleven insular cases were identified, five of them with an anterior insular seizure onset and six with a posterior one. Nonpainful somatosensory symptoms and autonomic symptoms were the most common symptoms (73% of patients) followed by speech-related symptoms (55%) and ipsilateral eye blinking (45%). Six patients had seizures restricted to somatosensory or viscerosensory symptoms. In all patients, seizures progressed to motor symptoms. Somatosensory symptoms did not differentiate anterior from posterior insular seizures. However, hyperkinetic signs, speech modifications, and viscerosensory symptoms were related to an anterior insular seizure-onset zone. Pain, asymmetric tonic, focal clonic, and tonic symptoms were more frequent in patients with a posterior insular seizure onset. Conclusions Seizure semiology is heterogeneous in pure insular-onset epilepsy. Differences between the anterior and posterior insular seizures reflect the functional organization of the insula. Particularly, the different types of motor symptoms may help to distinguish anterior from posterior insular seizure onset.

International audience; Management of patients after initial epilepsy surgical failure is challenging. In this study, we report our experience in using the stereoelectroencephalography (SEEG) method in the reevaluation of patients after initial epilepsy surgical failure. We selected 28 patients examined through SEEG in our department for drug-resistant focal epilepsy following initial epilepsy surgical failure. For each patient, the residual seizure onset zone (rSOZ) as defined by SEEG was classified as either contiguous if the seizure onset zone (SOZ) was focal and close to the surgical cavity (same lobe) or noncontiguous in cases where the SOZ included site(s) distant from the surgical cavity. The rSOZ was defined according to visual analysis of SEEG traces completed by an estimation of the epileptogenicity index (EI). A second surgical procedure was performed in 12 patients (45%). A favorable outcome (Engel class I or II) was obtained in 9/12 patients (6 in Engel class I, 50%). The proportion of patients that had reoperation was higher in the contiguous group (80%) than in the noncontiguous group (22%) (p = 0.02). A rSOZ localized in close relation to the initial surgical resection zone (contiguous group) was found in 10 patients (35%). Among them, 8 have since undergone reoperation, and a good outcome (Engel class I) was achieved in 5/8 (63%). A rSOZ involving a distant region from the first surgery was observed in 18 patients (65%) (noncontiguous group). Among them, only 4 have undergone reoperation, leading to a failure in 2 (Engel class III or IV) and a good outcome in 2 (IA). Ten patients had a first standard temporal lobectomy, and in 50% of these cases, the insula was involved in the rSOZ. Stereoelectroencephalography offers a unique way to evaluate the rSOZ at the individual level and thus guide further surgical decision-making. The best results are observed in patients having a focal rSOZ close to the site of the surgical resection in the first surgery.

OBJECTIVEHemispherotomy is currently the most frequently performed surgical option for refractory epilepsy associated with large perinatal or childhood ischemic events. Such an approach may lead to good seizure control, but it has inherent functional consequences linked to the disconnection of functional cortices. The authors report on 6 consecutive patients who presented with severe epilepsy associated with hemiplegia due to stroke and who benefitted from a new, stereoelectroencephalography-guided partial disconnection technique.METHODSThe authors developed a new disconnection technique termed “tailored suprainsular partial hemispherotomy” (TSIPH). Disconnection always included premotor and motor cortex with variable anterior and posterior extent.RESULTSAt a mean follow-up of 28 months, there were no deaths and no patient had hydrocephalus. Motor degradation was observed in all patients in the 2 weeks after surgery, but all patients completely recovered. The 6 patients were seizure free (Engel class IA) at the last follow-up. No neuropsychological aggravation was observed.CONCLUSIONSTSIPH appears to be a conservative alternative to classic hemispherotomy, leading to favorable outcome in this series.

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.

Summary The pathophysiological mechanisms of epileptic spasms are still poorly understood. The role of subcortical structures has been suggested on the basis of non-localized EEG features and from experimental data. The description of asymmetric spasms associated with lateralized EEG patterns has challenged this view and raises the possibility of a cortical origin. This study investigated the cortical organization of partial seizures associated with epileptic spasms in children undergoing intracerebral EEG recordings for presurgical evaluation. Eleven children with drug resistant epileptic spasms and for whom depth electrode recordings were performed were retrospectively studied. In all children several features suggested a focal origin. Cortical involvement was studied using the "Epileptogenicity Index" (EI). A focal origin was finally demonstrated in 10/11 patients. Seven patients demonstrated pre-ictal changes in the seizure onset zone area. EI analysis showed maximal values in the temporal ( n =5), parietal ( n =1) or frontal ( n =5) cortices. EEG changes were also observed in the premotor cortex during spasms in patients with frontal or parietal seizures and in 3/5 patients with temporal lobe seizures. Good surgical outcome (class I or II) was obtained in 7/10 patients. Seizures associated with epileptic spasms may originate from various cortical regions. Premotor/motor cortices are probably involved in determining ictal clinical changes.

Introduction L‘hemispherotomie verticale para sagittale decrite par O. Delalande est un geste neurochirurgical de deconnection hemispherique. Elle est indiquee dans le traitement des epilepsies refractaires dont la zone epileptogene est largement etendue sur un hemisphere. Nous rapportons notre experience des dix dernieres annees. Materiel et methodes Entre 2008 et 2018, 11 patients (6 filles et 5 garcons) ont beneficie d’une hemispherotomie verticale para sagittale pour une epilepsie refractaire au traitement medicamenteux bien conduit dans le service de Neurochirurgie pediatrique de Marseille. Tous les patients ont beneficie d’un bilan pre operatoire complet (EEG, Video EEG, Pet Scan, IRM, Bilan neuropsychologique) et ont ete discute en reunion multidisciplinaire de chirurgie de l’epilepsie pediatrique. Tous les enfants ont beneficie de la technique de Delalande. Ils ont ete revus en consultation a 1 mois, 6 mois puis de facon annuelle. Tous ont beneficie d’un examen anatomopathologique sur le cortex reseque. Resultats Sur les 11 enfants, 4 presentaient une encephalite de Rasmussen (36,4 %), 4 autres souffraient d’une hemimegalencephalie (36,4 %), 2 presentaient une dysplasie corticale etendue (18,2 %) enfin un enfant presentait une epilepsie secondaire a un accident vasculaire cerebrale ischemique. Tous les patients ont eu une remission complete postoperatoire immediate des manifestations epileptiques, dont 8 (72,8 %) restent stables pendant le suivi. Pour les autres 3 patients (27,3 %), on a note une re-apparition des crises a distance durant le suivi (18–36 mois postoperatoire). Un patient a ete repris au bloc operatoire pour une deconnexion incomplete, avec une remission totale des crises apres le geste complementaire. Les complications postoperatoires sont centrees sur l’hemiparesie controlaterale, presente chez 100 % des enfants. le deficit predomine a distance sur le membre superieur. Nous n’avons pas enregistre d’hydrocephalies postoperatoires. Deux patients (18,2 %) ont presente une collection sous-durale homolaterale, traitee par une derivation sous-duro-peritoneale, avec une bonne evolution. Ces HSD nous ont conduits a modifier notre technique operatoire. Conclusion L’hemispherotomie verticale para sagittale est un traitement efficace des epilepsies refractaires hemispheriques. Elle permet un controle complet des crises chez la majorite des enfants et une qualite de vie optimale. La recidive de crises a distance doit faire envisager une deconnexion incomplete et envisager un second temps chirurgical. Les HSD peuvent etre eviter par une modification simple de la technique.

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

International audience; Early onset epileptic encephalopathies (EOEE) are heterogeneous group of severe epilepsies that still need to be better defined and characterized. On a genetic point of view, several dozen of genes have been associated with EOEE, and to date, it is difficult to find a common mechanism to explain EOEE. In this short review, we show that two mains genes are involved in EOEE: STXBP1 and KCNQ2. Focusing on KCNQ2 related EOEE, we show that a relatively similar phenotype can be related to various consequences of mutations on a single gene. This will probably challenge the treatment of EOEE patients.

Resume Objectif Les maladies mitochondriales par deficit de la chaine respiratoire regroupent des atteintes heterogenes multiviscerales. L’atteinte neurologique, en particulier l’epilepsie, est tres frequente chez l’enfant. L’objectif de cette etude etait de rechercher des criteres cliniques permettant devant une epilepsie de s’orienter vers une pathologie mitochondriale. Methode Il s’est agi d’une etude retrospective portant sur des enfants epileptiques ayant eu une biopsie musculaire ou hepatique entre 1995 et 2010 dans le but de rechercher une maladie mitochondriale. Les patients ont ete repartis en 2 groupes en fonction des resultats : groupe 1 (presence d’un dysfonctionnement de la chaine respiratoire mitochondriale) versus groupe 2 (absence de pathologie mitochondriale). Le phenotype epileptique a ete compare entre les 2 groupes. Dans le groupe 1, nous avons precise le phenotype clinique des patients ainsi que le type d’atteinte mitochondriale. Resultats Cinquante-trois enfants ont ete inclus : 29 dans le groupe 1 et 24 dans le groupe 2. L’âge moyen de debut de l’epilepsie etait de 39,6 mois dans le groupe 1 versus 11,8 mois dans le groupe 2. Dans le groupe 1, les epilepsies etaient moins pharmacoresistantes et plus associees a d’autres signes cliniques. Conclusion L’epilepsie n’apparait pas comme un signe isole de maladie mitochondriale. Elle apparait le plus souvent au cours de la 2 nde annee de vie et de nombreuses autres atteintes d’organes sont presentes, notamment neurosensorielles (ophtalmologiques a type d’apraxie oculomotrice, atrophie optique, retinite pigmentaire ; auditives comme une surdite, une hypo-acousie) et hepatiques (cytolyse hepatique, hepatomegalie). En revanche, chez les enfants ne presentant pas de pathologie mitochondriale, l’epilepsie a un debut souvent plus precoce (avant l’âge de 3 mois), elle est isolee sans atteinte d’organes associee, generalement pharmacoresistante et s’integre dans un tableau d’encephalopathie lie le plus souvent a des mutations de certains genes de developpement qu’il faut savoir rechercher.

Resume Objectif L’association diabete de type 1 et epilepsie est connue. Cependant, la physiopathologie de cette association demeure incomprise. L’objectif de cette etude etait de decrire l’epilepsie associee au diabete de type 1 chez l’enfant. Patients et methodes Etude retrospective de tous les patients suivis au CHU La Timone a Marseille pour une epilepsie et un diabete de type 1. Pour chaque patient, nous avons etudie le type d’epilepsie et ses caracteristiques electrocliniques et radiologiques, le type de diabete (caracteristiques biologiques, equilibre) et l’âge de decouverte de ces 2 affections. Resultats Dix enfants ont ete etudies. Parmi eux, 5 presentaient une epilepsie generalisee (4 idiopathiques, 1 non idiopathique) et 5 une epilepsie partielle (4 non idiopathiques a localisation majoritairement temporale, 1 idiopathique). Dans la majorite des cas, les autoanticorps anti-glutamique acide decarboxylase (GAD) etaient presents et l’epilepsie etait survenue secondairement au diabete. Conclusion Les 2 types d’epilepsie les plus frequents dans cette association sont les epilepsies generalisees idiopathiques et les epilepsies partielles non idiopathiques temporales. Plusieurs mecanismes pourraient etre impliques (immunitaire, desequilibre glycemique, genetique).

This review focuses on so-called "periodic syndromes of childhood that are precursors to migraine," as included in the second edition of the International Classification of Headache Disorders. Presentation is characterized by an episodic pattern and intervals of complete health. Benign paroxysmal torticollis is characterized by recurrent episodes of head tilt, secondary to cervical dystonia, with onset between ages 2-8 months. Benign paroxysmal vertigo presents as sudden attacks of vertigo lasting seconds to minutes, accompanied by an inability to stand without support, between ages 2-4 years. Cyclic vomiting syndrome is distinguished by its unique intensity of vomiting, affecting quality of life, whereas abdominal migraine presents as episodic abdominal pain occurring in the absence of headache. Their mean ages of onset are 5 and 7 years, respectively. Diagnostic criteria and appropriate evaluation represent the key issues. Therapeutic recommendations include reassurance, lifestyle changes, and prophylactic as well as acute antimigraine therapy.

International audience; BACKGROUND: Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is a frequent and severe cause of encephalitis in children with potential efficient treatment (immunotherapy). Suggestive clinical features are behavioural troubles, seizures and movement disorders. Prompt diagnosis and treatment initiation are needed to guarantee favourable outcome. Nevertheless, diagnosis may be challenging because of the classical ancillary test (magnetic resonance imaging (MRI), electroencephalogram, standard cerebro-spinal fluid analysis) have limited sensitivity. Currently, immunological analyses are needed for the diagnostic confirmation. In adult patients, some studies suggested a potential role of cerebral (18)FluoroDeoxy-Glucose Positron Emission Tomography (FDG-PET) in the evaluation of anti-NMDAR encephalitis. Nevertheless, almost no data exist in paediatric population.ăMETHOD: We report retrospectively clinical, ancillary tests and cerebral FDG-PET data in 6 young patients (median age=10.5 years, 4 girls) with immunologically confirmed anti-NMDAR encephalitis.ăRESULTS: Our patients presented classical clinical features of anti-NMDAR encephalitis with severe course (notably four patients had normal MRI). Our series shows the feasibility and the good sensitivity of cerebral FDG-PET (6/6 patients with brain metabolism alteration) in paediatric population. We report some particular features in this population: extensive, symmetric cortical hypometabolism especially in posterior areas; asymmetric anterior focus of hypermetabolism; and basal ganglia hypermetabolism. We found also a good correlation between the clinical severity and the cerebral metabolism changes. Moreover, serial cerebral FDG-PET showed parallel brain metabolism and clinical improvement.ăCONCLUSION: Our study reveals the existence of specific patterns of brain metabolism alteration in anti-NMDAR encephalitis in paediatric population.

Mutations of SCN4A encoding the skeletal muscle sodium channel Nav 1.4 cause several types of disease, including sodium channel myotonias. The latter may be responsible for neonatal symptoms, including severe neonatal episodic laryngospasm (SNEL). Establishing the diagnosis of SCN4A-related SNEL early in the neonatal period is crucial because treatment is available that can reduce laryngospasm and improve vital and cerebral outcome. We report 2 new unrelated French patients who presented with SNEL. The first patient was initially diagnosed with laryngomalacia and underwent laryngeal surgery in the neonatal period before being diagnosed with myotonia at 14 months of age. The episodes of laryngospasm disappeared spontaneously, although occasional circumstances such as cold exposure could trigger laryngeal reactions; in addition, he developed myotonia corresponding to an adult myotonia permanens phenotype. This patient is now 24 years old and leading a normal life. The second patient was initially diagnosed with gastroesophageal reflux, then SNEL; his condition improved with carbamazepine treatment, and he is now 6 months old. The diagnostic sequence in both patients was the same: first, severe episodic apneic attacks necessitating hospitalization occurring in the first week of life; second, observation of muscle hypertrophy and peripheral hypertonia with a clear myotonic pattern on electromyogram (at 14 and 3 months of age, respectively); third, genetic testing revealing de novo SCN4A G1306E mutation. Both patients have had good therapeutic response to sodium channel blockers (carbamazepine or mexiletine).

In order to assess the cognitive and adaptive profiles of school-aged patients with Dravet syndrome (DS), we proposed to evaluate the intelligence and adaptive scores in twenty-one 6- to 10-year-old patients with DS followed in our institution between 1997 and 2013. Fourteen patients were tested using the Wechsler Intelligence Scale for Children (WISC) and the Vineland Adaptive Behavioral Scales (VABS); 6 patients could not be tested with the WISC and were tested with the VABS only, and one was tested with the WISC only. Data regarding the epilepsy were retrospectively collected. Statistical analysis (Spearman rank order and Pearson correlation coefficient) was used to correlate early epilepsy characteristics with the cognitive and adaptive scores. Sodium channel, neuronal alpha-subunit type 1 (SCN1A) was mutated in 19 out of 21 patients. After the age of 6 years, none of the DS patients had a normal intelligence quotient (IQ) using WISC (age at the testing period: mean = 100 ± 5; median = 105 months; mean total IQ = 47 ± 3; n = 15). Only five patients had a verbal and/or a non verbal IQ of more than 60 (points). Their cognitive profile was characterized by an attention deficit, an inability to inhibit impulsive responses, perseverative responses and deficit in planning function. Administering the Vineland Adaptive Behavioral Scales in the same period, we showed that socialization skills were significantly higher than communication and autonomy skills (age at the testing period: mean = 100 ± 4; median = 100 months; n = 20). We did not find any significant correlation between the IQ or developmental quotient assessed between 6 and 10 years of age and the quantitative and qualitative parameters of epilepsy during the first two years of life in this small group of patients. Despite an overall moderate cognitive deficit in this group of patients, the Vineland Adaptive Behavioral Scales described an adaptive/behavioral profile with low communication and autonomy capacities, whereas the socialization skills were more preserved. This profile was different from the one usually found in young patients with autism and may require specific interventions.

Introduction Une crise d’epilepsie est un signe frequent inaugural d’un accident vasculaire cerebral chez l’enfant. Vingt-cinq pour cent de ces enfants vont presenter une epilepsie. La frequence de l’epilepsie refractaire varie de 0 a 6O % dans la litterature. L’hemispherotomie fonctionnelle est actuellement le « gold standard » lors de la prise en charge neurochirurgicale. Nous rapportons pour la premiere fois notre experience de deconnexion sus-insulaire guidee par SEEG des aires « centrales » chez ces enfants. Materiels et methode Suivi prospectif. 2 enfants de 12 et 13 ans. Epilepsie refractaire evoluant depuis 6 ans pour l’un et 5 ans pour l’autre suite a un AVC ischemique sylvien etendu, de cause inconnue malgre un bilan exhaustif. Un bilan complet pre chirurgical a ete realise associant, EEG, video–EEG, champ visuel, Pet TDM, IRM morphologique et fonctionnelle ainsi qu’un bilan neuropsychologique. La frequence des crises est variable, pluri quotidiennes chez la fille et pluri-hebdomadaires pour le garcon. Les chutes sont frequentes avec presence de traumatismes violents retrouves dans l’historique. Une SEEG sans cadre controlee par la neuronavigation a ete realisee chez les 2 enfants dans l’idee de realiser une deconnexion fonctionnelle epargnant les regions non epileptogenes. Resultats Pour ces 2 enfants, la SEEG a permis de visualiser plusieurs crises habituelles. La zone ZE a pu etre delimitee par correlations electro-cliniques et confirmee par le calcul de l’index d’epileptogenicite sur les differentes electrodes impliquees. La ZE etait a chaque fois centree par le foyer ischemique et entourait le sillon central. Nous avons implante 11 electrodes chez le garcon et 12 chez la fille. Il n’y avait aucun argument pour une ZE temporale ou occipitale associee. Le bilan neuropsychologique restait dans la normale faible. Une deconnexion sus insulaire de la ZE a ete realisee. Les 2 enfants sont classes actuellement Engel 1 avec un suivi moyen de 11 mois. L’hemiplegie post-operatoire a recupere en 3 semaines. Les 2 enfants ont ameliore leur autonomie et ont repris une scolarisation normale avec AVS. La diminution des traitements oraux a ete debutee. Conclusion La deconnexion sus insulaire guidee par SEEG de la ZE permet une deconnexion respectant au mieux les regions saines et les grands faisceaux de substance blanche. Elle nous parait representer une veritable alternative fonctionnelle a l’hemispherotomie chez ces enfants. La preservation des structures occipitales et temporales doit ameliorer la qualite de vie de ces enfants et probablement leurs resultats scolaires. L’etude SEEG est un imperatif dans la prise de decision. Nous rapportons les 2 premiers cas de deconnexion sus insulaire de la ZE chez des enfants presentant une epilepsie refractaire apres AVC ischemique sylvien large. Ces resultats doivent etre confirmes a l’avenir.

Les encephalites avec anticorps anti-recepteur NMDA sont caracterisees par l’installation sub-aigue de troubles psychiatriques, d’alteration de la conscience et mouvements anormaux paroxystiques. Les anticorps diriges contre les recepteurs NMDA sont retrouves dans le LCR des patients, parfois egalement dans le serum. La presence de crises d’epilepsie est classiquement rapportee, mais leur caracterisation electro-clinique est peu decrite. Nous rapportons les observations de deux patientes de 10 et 14 ans avec une telle encephalite chez qui nous decrivons les caracteristiques electro-cliniques, l’imagerie morphologique et fonctionnelle, les donnees neuropsychologiques et l’evolution sous traitement specifique. Une des patientes presentait des phenomenes paroxystiques, initialement pris pour des crises ayant pu etre enregistres en video-EEG. Il s’agit de phenomenes dystoniques axiaux et oro faciaux paroxystiques prolonges, avec cyanose, mais dont l’origine epileptique a pu etre exclue. Ainsi, les «crises» rapportees chez les patients avec encephalite a anticorps anti-NMDA ne sont pas toutes de nature epileptique. L’existence de phenomenes dystoniques paroxystiques non epileptiques doit etre connue. Leur reconnaissance peut permettre une meilleure prise en charge therapeutique symptomatique.

L’epilepsie est 2 a 3 fois plus frequente chez les enfants diabetiques de type 1. Cette association non fortuite a deja ete rapportee cependant son origine demeure inconnue : genetique, immunitaire… Nous presentons une serie de 10 cas suivis de facon retrospective afin de decrire les diverses manifestations epileptiques et diabetiques de ces patients et leurs caracteristiques electro-cliniques. La majorite des patients ont une epilepsie des regions centrales, avec des crises prolongees, voire dans un cas une epilepsie partielle continue revelatrice du diabete. Les autoanticorps anti-GAD retrouves dans la majorite des diabete de type 1, ont ete suggeres pour etre le lien entre l’epilepsie et le diabete de type 1. En effet, la GAD est retrouvee dans les cellules beta du pancreas mais c’est aussi une enzyme clef dans la synthese du GABA qui est le principal neurotransmetteur inhibiteur dans le systeme nerveux central. Le dysfonctionnement de la GAD cerebrale pourrait perturber la synthese du GABA et expliquer la plus grande frequence de l’epilepsie chez les patients diabetiques.