Search

Objective To further delineate the electroclinical features of individuals with SYNGAP1 pathogenic variants. Methods Participants with pathogenic SYNGAP1 variants and available video-electroencephalogram (EEG) recordings were recruited within five European epilepsy reference centers. We obtained molecular and clinical data, analyzed EEG recordings and archived video-EEGs of seizures and detailed characteristics of interictal and ictal EEG patterns for every patient. Results We recruited 15 previously unreported patients and analyzed 72 EEGs. Two distinct EEG patterns emerged, both triggered by eye closure. Pattern 1 (14/15 individuals) consisted of rhythmic posterior/diffuse delta waves appearing with eye-closure and persisting until eye opening (strongly suggestive of fixation-off sensitivity). Pattern 2 (9/15 individuals) consisted of diffuse polyspike-and-wave discharges triggered by eye closure (eye-closure sensitivity). Both patterns presented in 8/15. Including archived video-EEG clips of seizures from 9/15 patients, we analyzed 254 seizures. Of 224 seizures experienced while awake, 161 (72%) occurred at or following eye closure. In 119/161, pattern 1 preceded an atypical absence, myoclonic seizure or myoclonic absence; in 42/161, pattern 2 was associated with eyelid myoclonia, absences and myoclonic or atonic seizures. Conclusions Fixation-off and eye closure were the main triggers for seizures in this SYNGAP1 cohort. Significance Combining these clinical and electroencephalographic features could help guide genetic diagnosis.

Purpose We aimed to identify prognostic factors for survival and long-term intellectual and developmental outcome in neonatal patients with early-onset urea cycle disorders (UCD) experiencing hyperammonaemic coma. Methods We retrospectively analysed ammonia (NH3) and glutamine levels, electroencephalogram and brain images obtained during neonatal coma of UCD patients born between 1995 and 2011 and managed at a single centre and correlated them to survival and intellectual and developmental outcome. Results We included 38 neonates suffering from deficiencies of argininosuccinate synthetase (ASSD, N = 12), ornithine transcarbamylase (OTCD, N = 10), carbamoylphosphate synthetase 1 (CPSD, N = 7), argininosuccinate lyase (ASLD, N = 7), N-acetylglutamate synthase (NAGS, N = 1) or arginase (ARGD, N = 1). Symptoms occurred earlier in mitochondrial than in cytosolic UCD. Sixty-eight percent of patients survived, with a mean (standard deviation-SD) follow-up of 10.4 (5.3) years. Mortality was mostly observed in OTCD (N = 7/10) and CPSD (N = 4/7) patients. Plasma NH3 level during the neonatal period, expressed as area under the curve, but not glutamine level was associated with mortality (p = .044 and p = .610). 62.1% of the patients had normal intellectual and developmental outcome. Intellectual and developmental outcome tended to correlate with UCD subtype (p = .052). No difference in plasma NH3 or glutamine level during the neonatal period among developmental outcomes was identified. EEG severity was linked to UCD subtypes (p = .004), ammonia levels (p = .037), duration of coma (p = .043), and mortality during the neonatal period (p = .020). Status epilepticus was recorded in 6 patients, 3 of whom died neonatally, 1 developed a severe intellectual disability while the 2 last patients had a normal development. Conclusion UCD subtypes differed by survival rate, intellectual and developmental outcome and EEG features in the neonatal period. Hyperammonaemia expressed as area under the curve was associated with survival but not with intellectual and developmental outcome whereas glutamine was not associated with one of these outcomes. Prognostic value of video-EEG monitoring and the association between status epilepticus and mortality should be assessed in neonatal hyperammonaemic coma in further studies.

Seizures caused by beta-lactam antibiotics are relatively rare. However, they represent a clinically significant phenomenon and have been widely reported in all age groups. Here we describe two infants presenting subtle multifocal seizures with a migrating aspect on EEG during beta-lactam antibiotic treatment with agents from the carbapenem group (meropenem) and the cephalosporin group (ceftazidime).

Background and aims Phospholipase A2 associated neurodegeneration (PLAN) is a heterogeneous autosomal recessive disorder caused by mutations in the ubiquitously expressed PLA2G6 gene. It is responsible for delayed brain iron accumulation and induces progressive psychomotor regression. We report the concomitant clinical, radiological and neurophysiological findings in PLAN patients in an attempt to determine the contribution of each test to guide diagnosis. Methods Concomitant clinical, radiological, electroencephalographic (EEG) and electrodiagnostic testing (EDX) findings in a series of 8 consecutive genetically confirmed PLAN patients were collected. Results All patients presented marked motor axonal loss, with decreased or absent distal compound muscle action potentials, acute and chronic denervation at needle electromyography, in contrast with preservation of sensory conduction. EEG showed high-amplitude fast activity in all patients aged above 15 months. Two patients showing severe neonatal hypotonia displayed atypical hypsarhythmia and epileptic spasms. Iron deposition in globus pallidus was observed in only two patients aged above 6 years. Conclusions Peripheral involvement is an early feature in PLAN recognizable by EDX at an earlier stage than typical iron accumulation in the brain. Furthermore, the association of West syndrome and axonal motor neuropathy may represent positive clues in favor of PLAN. This results emphasize the interest of early and repeated EDX.

Purpose Sturge-Weber syndrome (SWS) is a neurocutaneous disorder characterized by a facial port-wine stain, a glaucoma, and a leptomeningeal angioma. Epilepsy occurs in more than 75% of affected children, and seizures occurring in the first year of life are associated with a poor neurological prognosis. The aim of this study was to identify possible predictive markers of epilepsy on electroencephalogram (EEG) performed prior to seizure onset in children with SWS. Methods This study included children with a diagnosis of SWS who had an EEG performed prior to seizure onset. Patients who did not develop epilepsy had a minimum follow-up of 3-years. We compared EEG characteristics of patients who developed epilepsy with patients who did not develop epilepsy by the time of their follow-up. Results Eleven children were included in this study. EEG was performed at the median age of 2.1 months (range 1.0–22.1). Six children developed seizures with a time interval between EEG and seizure onset ranging from 2 days to 21 months. EEG background activity was asymmetric in 8 patients, 5 of whom later developed epilepsy. Focal interictal spikes or sharp waves were exclusively recorded in patients who developed later epilepsy (4 out of 6). One of these patients had a supposed false positive EEG as he did not developed epilepsy until 21 months later and one patient had a false negative EEG with seizures occurring 2 days after a normal EEG. Conclusion Spikes on EEG might be a useful marker to identify patients with SWS at risk of developing epilepsy. Their predictive value should be assessed in larger prospective studies.

Objectives Little is known about off-label use and manipulations to achieve the prescribed dose of antiepileptic drugs (AEDs) in outpatient prescriptions. This study aimed to evaluate this practice in a tertiary center for child epilepsy. Methods We reviewed off-label use and manipulations of AEDs delivered to the outpatient's epilepsy clinic. Multivariate logistic regressions were used to determine the factors associated with off-label and manipulated uses. Results Five hundred eleven consultations generated 897 AED deliveries (1.75/consultation). Off-label use involved 182 (20.3%) of prescribed AEDs. Factors associated with off-label use were polytherapy and new AEDs while increase of age and nondevelopmental and structural–metabolic etiologies have a protective effect. Among the 1725 doses of AEDs prescribed per day, 33.5% generated manipulations (n = 582): 40% inadequate (n = 237) and 60% adequate (203 syrups, 112 scored tablets, 30 drops medicine). Polytherapy (p Conclusion Off-label use and manipulations of AEDs remain an important problem in home care of children with epilepsy. This is mainly a concern for the most vulnerable groups, i.e., young patients, patients undergoing polytherapy, and patients with developmental and epileptic encephalopathy (DEE). International initiatives have been launched to improve the availability of labeled and adapted drugs in this population.

Background Complement is likely to have a role in refractory generalised myasthenia gravis, but no approved therapies specifically target this system. Results from a phase 2 study suggested that eculizumab, a terminal complement inhibitor, produced clinically meaningful improvements in patients with anti-acetylcholine receptor antibody-positive refractory generalised myasthenia gravis. We further assessed the efficacy and safety of eculizumab in this patient population in a phase 3 trial. Methods We did a phase 3, randomised, double-blind, placebo-controlled, multicentre study (REGAIN) in 76 hospitals and specialised clinics in 17 countries across North America, Latin America, Europe, and Asia. Eligible patients were aged at least 18 years, with a Myasthenia Gravis-Activities of Daily Living (MG-ADL) score of 6 or more, Myasthenia Gravis Foundation of America (MGFA) class II-IV disease, vaccination against Neisseria meningitides, and previous treatment with at least two immunosuppressive therapies or one immunosuppressive therapy and chronic intravenous immunoglobulin or plasma exchange for 12 months without symptom control. Patients with a history of thymoma or thymic neoplasms, thymectomy within 12 months before screening, or use of intravenous immunoglobulin or plasma exchange within 4 weeks before randomisation, or rituximab within 6 months before screening, were excluded. We randomly assigned participants (1:1) to either intravenous eculizumab or intravenous matched placebo for 26 weeks. Dosing for eculizumab was 900 mg on day 1 and at weeks 1, 2, and 3; 1200 mg at week 4; and 1200 mg given every second week thereafter as maintenance dosing. Randomisation was done centrally with an interactive voice or web-response system with patients stratified to one of four groups based on MGFA disease classification. Where possible, patients were maintained on existing myasthenia gravis therapies and rescue medication was allowed at the study physician's discretion. Patients, investigators, staff, and outcome assessors were masked to treatment assignment. The primary efficacy endpoint was the change from baseline to week 26 in MG-ADL total score measured by worst-rank ANCOVA. The efficacy population set was defined as all patients randomly assigned to treatment groups who received at least one dose of study drug, had a valid baseline MG-ADL assessment, and at least one post-baseline MG-ADL assessment. The safety analyses included all randomly assigned patients who received eculizumab or placebo. This trial is registered with ClinicalTrials.gov, number NCT01997229. Findings Between April 30, 2014, and Feb 19, 2016, we randomly assigned and treated 125 patients, 62 with eculizumab and 63 with placebo. The primary analysis showed no significant difference between eculizumab and placebo (least-squares mean rank 56·6 [SEM 4·5] vs 68·3 [4·5]; rank-based treatment difference -11·7, 95% CI -24·3 to 0·96; p=0·0698). No deaths or cases of meningococcal infection occurred during the study. The most common adverse events in both groups were headache and upper respiratory tract infection (ten [16%] for both events in the eculizumab group and 12 [19%] for both in the placebo group). Myasthenia gravis exacerbations were reported by six (10%) patients in the eculizumab group and 15 (24%) in the placebo group. Six (10%) patients in the eculizumab group and 12 (19%) in the placebo group required rescue therapy. Interpretation The change in the MG-ADL score was not statistically significant between eculizumab and placebo, as measured by the worst-rank analysis. Eculizumab was well tolerated. The use of a worst-rank analytical approach proved to be an important limitation of this study since the secondary and sensitivity analyses results were inconsistent with the primary endpoint result; further research into the role of complement is needed. Funding Alexion Pharmaceuticals.

Objectives To describe the semiology and EEG characteristics of the age-related pattern of sleep/nocturnal (S/N) seizures in patients with Dravet Syndrome (DS). Methods We retrospectively analysed the clinical and EEG data of DS patients followed at our reference centre for Rare Epilepsies. We included patients aged two years and older who fulfilled clinical and EEG criteria of DS (ILAE 1989). Genetic testing for SCN1A was done in all, followed by PCDH19 if this was negative. Patients showing a genetic abnormality in PCDH19 were excluded. Of 73 DS patients followed at our centre, 26 (15 males and 11 females), called the S/N group, experienced a switch in the circadian rhythm of seizures, from mainly awake/diurnal to mainly S/N seizures. We retrospectively analysed their clinical, EEG and genetic data. We have compared them to a second group of 7 patients (4 males and 3 females), aged more than 11 years, the non-S/N group, who did not develop S/N seizures. Results We observed a pattern of S/N seizures concomitant with a decrease of awake seizures between 4 and 11 years (median 6 years 6 months). S/N seizures were brief but often occurred in clusters of 2–15 per night. Seizures were mostly focal (26) with frontal-central onset (25) and tonic or tonic-vibratory in semiology. S/N seizure clusters were difficult to control despite many AEDs trials. Benzodiazepines reduced seizure recurrence within a cluster in some patients. While no significant differences were found between groups regarding clinical features, the presence of frontal and central anomalies on wake and sleep EEG was significantly associated with the presence of the S/N pattern. Conclusions Patients with DS often develop a characteristic clinical and EEG pattern with S/N tonic and tonic clonic seizures that is often underdiagnosed. Seizure semiology and EEG pattern differ from LGS but may worsen the quality of sleep of such patients and their families. The possible role of this pattern in SUDEP occurring mainly during sleep and at the same age should be further explored. Current AEDs have limited efficacy and specific drug trials should be proposed.

To test whether an integrated passive and active aeration system could be an effective solution for aerobic decomposition of municipal waste in technical conditions, a full-scale composting reactor was designed. The waste was actively aerated for 5d, passively aerated for 35 d, and then actively aerated for 5d, and the entire composting process was monitored. During the 45-day observation period, changes in the fractional, morphological and physico-chemical characteristics of the waste at the top of the reactor differed from those in the center of the reactor. The fractional and morphological analysis made during the entire process of stabilization, showed the total reduction of organic matter measured of 82 wt% and 86 wt% at the respective depths. The reduction of organic matter calculated using the results of Lost of Ignition (LOI) and Total Organic Carbon (TOC) showed, respectively, 40.51-46.62% organic matter loss at the top and 45.33-53.39% in the center of the reactor. At the end of the process, moisture content, LOI and TOC at the top were 3.29%, 6.10% and 4.13% higher, respectively, than in the center. The results showed that application of passive aeration in larger scale simultaneously allows the thermophilic levels to be maintained during municipal solid waste composting process while not inhibiting microbial activity in the reactor.

Long-term video-EEG corresponds to a recording ranging from 1 to 24 h or even longer. It is indicated in the following situations: diagnosis of epileptic syndromes or unclassified epilepsy, pre-surgical evaluation for drug-resistant epilepsy, follow-up of epilepsy or in cases of paroxysmal symptoms whose etiology remains uncertain. There are some specificities related to paediatric care: a dedicated pediatric unit; continuous monitoring covering at least a full 24-hour period, especially in the context of pre-surgical evaluation; the requirement of presence by the parents, technician or nurse; and stronger attachment of electrodes (cup electrodes), the number of which is adapted to the age of the child. The chosen duration of the monitoring also depends on the frequency of seizures or paroxysmal events. The polygraphy must be adapted to the type and topography of movements. It is essential to have at least an electrocardiography (ECG) channel, respiratory sensor and electromyography (EMG) on both deltoids. There is no age limit for performing long-term video-EEG even in newborns and infants; nevertheless because of scalp fragility, strict surveillance of the baby's skin condition is required. In the specific context of pre-surgical evaluation, long-term video-EEG must record all types of seizures observed in the child. This monitoring is essential in order to develop hypotheses regarding the seizure onset zone, based on electroclinical correlations, which should be adapted to the child's age and the psychomotor development.

The aim was to localize the interictal cerebral perfusion abnormalities of focal cortical dysplasia (FCD) in children with Arterial Spin Labeling MRI (ASL) in a retrospective study of nine consecutive children explored with multimodal investigation during interictal periods. We analyzed brain morphology with a 1.5T MRI and a dedicated protocol for epilepsy. Brain perfusion was quantified with pseudo continuous ASL. Brain metabolism was imaged with (18)FDG-PET in six patients. Microvessel histology was studied in five children who underwent epilepsy surgery with CD34 immunostaining on FCD and control samples. Localized decrease of cerebral blood flow (CBF) was found on visual analysis in all patients with ASL. It was co-localized with the structural MRI abnormalities in every case, with PET hypo-metabolism in 5/6 cases, and with histologically proven FCD type IIb in 5/5 cases (all seizure free after surgery). CBF was lower (Kruskal-Wallis test, p=0.001) in FCD than in normal cortex. The total count of CD34+ microvessels was similar in FCD and control cases, but microvasculature showed disorganized architecture. Interictal ASL is a non-invasive method that may help to localize the epileptogenic zone showing hypo-perfusion in FCD. Whether this finding could be generalized to MRI-negative FCD needs to be further studied.

Electroencephalography allows the functional analysis of electrical brain cortical activity and is the gold standard for analyzing electrophysiological processes involved in epilepsy but also in several other dysfunctions of the central nervous system. Morphological imaging yields complementary data, yet it cannot replace the essential functional analysis tool that is EEG. Furthermore, EEG has the great advantage of being non-invasive, easy to perform and allows control tests when follow-up is necessary, even at the patient's bedside. Faced with the advances in knowledge, techniques and indications, the Societe de Neurophysiologie Clinique de Langue Francaise (SNCLF) and the Ligue Francaise Contre l'Epilepsie (LFCE) found it necessary to provide an update on EEG recommendations. This article will review the methodology applied to this work, refine the various topics detailed in the following chapters. It will go over the summary of recommendations for each of these chapters and underline proposals for writing an EEG report. Some questions could not be answered by the review of the literature; in those cases, an expert advice was given by the working and reading groups in addition to the guidelines

Objectives Neurological causes are common diagnoses for apparent life-threatening events in infants. The objective of this study was to evaluate the relevancy of electroencephalography performed after an apparent life-threatening event. Material and methods A retrospective study was conducted in a children's hospital over a 1-year period. The charts of infants under 2 years of age who were admitted following an apparent life-threatening event were reviewed. Clinical and biological data were collected and electroencephalograms - divided into normal and abnormal - were reviewed. To evaluate the follow-up state of the patients, parents were invited to complete an evaluation form an average 13 months after the event. The yield for electroencephalography was established according to the ratio of positive results contributing to the diagnosis of the cause of the apparent life-threatening event. Results A total of 47 patients met the inclusion criteria. Fifteen had had an EEG, 32 had not. The rate of abnormal neurological signs described by parents during the apparent life-threatening event was higher in the EEG group compared to the group without EEG (53% vs. 22%, P=0.05). In the follow-up, 35% of the children presented a second event, which was described as being similar or less impressive and occurred in the 1st month after the event (91%). Of the eight abnormal electroencephalograms, six had no specific abnormalities and two contributed to the diagnosis of epileptic seizure. Therefore, the diagnostic yield of electroencephalography in this study was 13% (2/8). Conclusions The yield of electroencephalography performed after an apparent life-threatening event is low. Neurological history and repeated physical examinations still remain the major diagnostic tools before resorting to electroencephalography.

Pendant le developpement prenatal et postnatal precoce, les activites electriques synchrones peuvent etre generees au sein des cortex sensoriels eux-memes, des structures sous-corticales ou etre evoquees par l’activite des organes sensoriels, elle-meme spontanee ou provoquee par les stimuli sensoriels. L’un des patterns EEG typique du premature, le « Delta-brush » (DB), qui associe une onde lente et des oscillations rapides, peut etre genere de facon spontanee ou etre evoque dans les cortex sensorimoteur, visuel et auditif par les mouvements et par les stimuli sensoriels correspondants. L’objectif de la presente etude, dediee aux reponses corticales aux stimuli auditifs (click), etait de preciser les caracteristiques spatio-temporelles des DBs evoques ainsi que leur rapport avec des potentiels evoques auditifs corticaux du premature tel que decrits anterieurement. Pour cela, les enregistrements EEG ont ete realises en haute resolution (32 electrodes) chez 30 nouveau-nes prematures de 30 a 38 semaines d’âge gestationnel sans risque neurologique et la position des electrodes a ete recalee sur des IRM 3D acquis chez d’autres prematures representatifs des âges etudies. L’analyse spectrale des reponses au click a montre une augmentation significative de la puissance spectrale dans une large bande des frequences, situee au niveau de la partie moyenne et posterieure du lobe temporal. Ces reponses du cortex temporal avaient une predominance droite, etaient plus amples dans le sommeil calme et diminuaient en puissance avec l’âge. Le moyennage des reponses a revele que la composante lente du DB etait une onde lente negative de grande amplitude qui culminait dans les regions temporales moyenne et posterieure successivement a 550 et 700 ms et correspondait au pole negatif d’un dipole s’inversant dans la region temporo-peri-sylvienne. Le DB evoque par les stimuli auditifs reflete probablement l’activite du cortex auditif et represente un biomarqueur potentiel du fonctionnement normal du cortex auditif chez le premature.

Due to the similarities between EEG activity of humans during second trimester of gestation and the activity patterns of neonatal rodents, the latter became valuable model to study the mechanisms by which early patterns of activity may act as template for later-emerging functional maps [2] . In rodents, early EEG activity (Spindles Bursts [SB]) are generated within a complex neural network including the peripheral sensory organs, subcortical nuclei as well as cortical areas. In the barrel cortex, sensory evoked SB contain early gamma oscillations (EGO) that are primarily driven by rhythmic gamma excitation from the thalamus and enable precise temporal binding of the topographically aligned thalamic and cortical neurons. EGO support long-term dependent potentiation in the thalamo-cortical synapses [1] . Characteristic preterm EEG patterns of “Delta-brushes” (DBs) are spontaneous EEG activities and have been reported in the sensory cortices following sensory stimuli and spontaneous movements. Spatiotemporal analyses of the cortical auditory-evoked responses (AERs) using 32-electrode EEG recordings in healthy neonates aged 30 to 38 post-menstrual weeks (PMW) showed that AERs are characterized by a power spectrum increase at frequency bands ranging from delta to gamma on the electrodes overlaying temporal regions. Time-frequency wavelet analysis also showed that fast (alpha-gamma) oscillations co-occurred with the auditory-evoked delta wave from around 650 ms after the stimulus and lasted for nearly 700 ms. Stimulus locked averaging disclosed cortical auditory-evoked potentials (CAEP) with negative high amplitude delta waves peaking successively over middle and posterior temporal regions. Thus, auditory-evoked DBs in preterm neonates are slow delta waves nesting fast oscillations in the temporal regions and correspond to the late part of CAEPs, which is lost when using classical CAEP processing [3] . Decreasing from 30 to 38 PMW, this EEG pattern is thus associated with the prenatal development of sensory processing circuits and likely participate to the cortical maps maturation.

SummaryDeveloping cortex generates endogenous activity that modulates the formation of functional units, but how this activity is altered to support mature function is poorly understood. Using recordings from the visual cortex of preterm human infants and neonatal rats, we report a “bursting” period of visual responsiveness during which the weak retinal output is amplified by endogenous network oscillations, enabling a primitive form of vision. This period ends shortly before delivery in humans and eye opening in rodents with an abrupt switch to the mature visual response. The switch is causally linked to the emergence of an activated state of continuous cortical activity dependent on the ascending neuromodulatory systems involved in arousal. This switch is sensory system specific but experience independent and also involves maturation of retinal processing. Thus, the early development of visual processing is governed by a conserved, intrinsic program that switches thalamocortical response properties in anticipation of patterned vision.

Resume Cette revue a pour but d'exposer la classification nosologique des « convulsions » neonatales, de preciser leurs causes, leur pronostic et de proposer une conduite diagnostique et therapeutique. Les crises peuvent etre de nature epileptique ou non, etre occasionnelles ou entrer dans le cadre d'une maladie epileptique ou metabolique. L'electroencephalogramme (EEG) a un role essentiel. En effet, il permet de confirmer le caractere epileptique des crises, d'en evaluer le pronostic, de guider le traitement et parfois de contribuer au diagnostic. Le bilan doit etre complete par l'imagerie (IRM) et par d'autres examens en fonction de l'orientation diagnostique. Il est essentiel d'aller le plus loin possible dans la recherche etiologique et de ne pas attribuer a une cause occasionnelle (en particulier a une encephalopathie anoxo-ischemique dont les criteres diagnostiques sont stricts) des convulsions d'autre origine, genetique ou en rapport avec une pathologie maternelle. Le traitement comprend plusieurs volets : le traitement de la cause des crises, le cas echeant celui des pathologies associees, le soutien des grandes fonctions vitales, et enfin le traitement antiepileptique. Il repose, pour les crises occasionnelles, en premier lieu, sur le phenobarbital, puis sur l'utilisation d'autres produits dont l'effet est immediat, et sur le pronostic a long terme demande a etre evalue de facon tres rigoureuse. A cote des crises occasionnelles, les syndromes epileptiques a debut neonatal et des maladies metaboliques sont une cause rare des crises neonatales. Les reconnaitre permet d'etablir le pronostic, de debuter rapidement un traitement approprie et specifique en fonction du syndrome epileptique et, quelques fois, de proposer un diagnostic antenatal. Les erreurs innees du metabolisme sont importantes a reconnaitre et necessitent une prise en charge urgente et specialisee. Un pronostic globalement mauvais, des convulsions neonatales dependent essentiellement de la cause des crises et, probablement aussi a un moindre degre, de leur persistance.

Metabolic disorders constitute an important cause of neurologic disease, including neonatal epilepsy. Epilepsy rarely dominates the clinical presentation, which is more frequently associated with other neurologic symptoms, such as hypotonia and/or vigilance disturbances. In most cases, epilepsy secondary to inherited metabolic disorders presents with polymorphic clinical and electrographic features that are difficult to classify into precise epileptic syndromes. However, specific types of seizures, such as myoclonic seizures or distinctive electroencephalographic patterns, such as suppression burst patterns, epileptic syndrome or early myoclonic encephalopathy, may suggest a specific metabolic disease. The aim of this article is to help clinicians in reviewing potential metabolic diagnoses and approaching metabolic evaluations.

Epilepsy is among the most frequent finding in many chromosome aberrations. While most chromosome aberrations can be associated with different seizure types, there are few aberrations which feature specific seizures and EEG patterns. Among the 400 different chromosomal imbalances described with seizures and EEG abnormalities, eight have a high association with epilepsy. These comprise: the monosomy 1p36, Wolf-Hirschhorn syndrome (4p-), Angelman syndrome, Miller-Dieker del 17p13.3, the inversion duplication 15 syndrome, ring 20 and ring 14 syndromes, Down's syndrome. These chromosomal regions where aberrations have an evident association with epilepsy may be useful targets for gene hunters. On the other hand, a better characterisation of epileptic syndrome in these disorders may lead to a better and specific treatment.

La plupart des crises neonatales sont occasionnelles : l’encephalopathie anoxo-ischemique (30–53 %), les atteintes vasculaires (AVC ou hemorragies intracrâniennes), les infections et les troubles metaboliques etant les causes les plus frequentes. Les malformations du developpement cortical et les syndromes epileptiques a debut neonatal representent moins de 15 % des etiologies [1] , [2] . L’objectif de notre etude retrospective etait de decrire l’EEG intercritique et les aspects electro-cliniques des crises chez le nouveau-ne a terme. Entre 2010 et 2015, 29 nouveau-nes hospitalises a l’hopital Necker–Enfants-Malades, ont eu des crises enregistrees en EEG-Video. Chez 27 enfants, les crises debutaient pendant la premiere semaine de vie. Les etiologies etaient : une encephalopathie anoxo-ischemique (6), une atteinte vasculaire (incluant les hemorragies intracrâniennes) (8), des maladies metaboliques (deficit en pyridoxal phosphate, acidurie methylmalonique, maladie peroxysomale) (3), des malformations du developpement cortical (incluant un hamartome du pedoncule cerebelleux) (7), une epilepsie neonatale benigne (2), une encephalopathie epileptique infantile precoce (EEIP) (1), et un « incontinentia pigmenti » (1). Il s’agissait le plus souvent de crises focales (24) avec des clonies focales enregistrees chez 14 enfants, tandis que 10 enfants presentaient des crises avec une symptomatologie plus fruste (troubles respiratoires, autres mouvements anormaux, deviation des yeux). Trois enfants ont presente des spasmes asymetriques et 2 avaient au moins 2 types de crises (spasmes ou des myoclonies suivies de crises focales). Le trace intercritique presentait un aspect de suppression-burst ou d’hemi-suppression-burst chez les enfants avec une EEIP et une hemimegalencephalie et etaient discontinus chez les enfants avec les maladies metaboliques. Dans l’encephalopathie anoxo-ischemique, les traces comportaient un aspect gravement altere ou etaient de type « intermediaire ». Dans les autres etiologies, les traces etaient bien organises et comportaient des anomalies focales (pointes lentes, ondes lentes, rythmes rapides, AVC, epilepsie neonatale benigne, malformation cerebrale focale, hemorragie intracrânienne). L’analyse de nos resultats confirme dans certains cas une excellente correlation deja connue entre les traces EEG et certains diagnostics etiologiques dont nous presentons les illustrations EEG-Video et les aspects typiques des traces intercritiques.

Objectives Hemiconvulsion-hemiplegia epilepsy (HHE) syndrome is a rare condition occurring in infancy and early childhood, characterized by prolonged clonic convulsions with unilateral predominance followed by ipsilateral hemiplegia during a febrile illness. After a free interval of variable duration, most patients develop epilepsy. HHE may occur either in patients with previous structural brain pathology or without any identified cause, so-called “idiopathic HHE”. We aimed to characterize the electro-clinical aspects observed in the acute phase and in the later course of the disease. Methods Between January 1997 and December 2016, 15 patients (8 girls, 7 boys), presenting with hemiconvulsion-hemiplegia were identified. Mean age was 10 years (range 3–21years) with a mean follow-up of 53 months (range 1–19 years). Electro-clinical features in the acute stage and evolution are described. Two patients died, one girl during the acute phase (on day 7). Results Median age at onset of convulsive status was 27.73 months (range 9–84 months). Status epilepticus lasted 30 minutes up to several days, and was characterized by unilateral clonic seizures in 10 patients and generalized seizures with unilateral predominance in 5 patients. In the acute phase interictal EEG disclosed inter-hemispheric asymmetry (14/15), background slowing (15/15), and spikes and slow sharp-waves (5/15). Seizures were recorded in 3 patients. Periodic lateralized epileptiform discharges were observed in one patient, who died during the acute phase on day 7. All patients presented ipsilateral hemiplegia (10/15 left, 5/15 right). The motor deficit (hemiplegia or hemiparesis) disappeared in 3 patients and persisted in 11, in two of them spastic hemiplegia developed. Eleven patients developed epilepsy after a free interval lasting up to 80 months, in 2 of them pharmaco-resistant. At the end of the observation period, all children with follow-up presented learning difficulties. Conclusion We describe electro-clinical features in the acute phase and in the later course in 15 patients presenting with HHE syndrome.

Purpose : To distinguish various types of childhood severe cryptogenic/idiopathic generalised epilepsy on the basis of reproducible diagnostic criteria, using multiple correspondence analysis (MCA). Methods : We applied MCA to a series of 72 children with no evidence of brain damage, starting epilepsy between 1 and 10 years, with two or more types of generalised seizures. We excluded patients with infantile spasms or typical absences. MCA was performed on all clinical and EEG parameters, first throughout follow-up, then restricted to the first year of the disease. Results : When including all follow-up variables, there were three groups: (1) Thirty-seven children with male predominance, familial history of epilepsy, simple febrile convulsions, massive myoclonus, tonic–clonic fits. Outcome was favourable, with no seizures and mildly affected cognitive functions. Interictal EEG showed short sequences of irregular 3-Hz spike-waves. (2) In 18 children, clinical characteristics were similar to those of the first group at the early stage, but 95% exhibited myoclonic status and vibratory tonic seizures, with persisting seizures on follow-up. EEG showed long sequences of generalised irregular spike and slow waves. Those two groups meet the characteristics of childhood onset myoclonic-astatic epilepsy (MAE) with respectively, favourable and unfavourable outcome. (3) Eleven children had later onset, atypical absences, tonic and partial seizures, and no myoclonus, or vibratory tonic seizures. All had mental retardation and persisting seizures. EEG showed long sequences of slow spike-wave activity and half the patients had spike and slow wave foci. These patients met the major characteristics of Lennox–Gastaut syndrome. Initial parameters failed to distinguish the first two groups, but Lennox–Gastaut syndrome (the third group) was distinct from both groups of myoclonic astatic epilepsy from the onset. Within MAE groups combined, clinical and EEG risk factors for mental retardation could be identified. Conclusion : It is possible to validate statistically the distinction between discrete epileptic syndromes. Myoclonic astatic epilepsy is therefore distinct from Lennox–Gastaut syndrome, and the distinction appears from the first year of the disorder.

Le myoclonus benin du sommeil calme (MBSC) est caracterise par la survenue de myoclonies non epileptiques, segmentaires plus ou moins rythmiques et synchrones, pendant le sommeil calme dans les premieres semaines de vie chez le nouveau-ne a terme sans antecedents particuliers. Nous avons analyse les caracteristiques cliniques et recherche d’eventuelles modifications de l’EEG et des PES chez 4 nouveau-nes presentant un MBSC enregistres en EEG-video avec polygraphie. Les myoclonies survenaient dans le sommeil calme de facon isolee ou en clusters et etaient facilitees par le bercement. Elles concernaient un a 4 membres, de facon plus ou moins rythmique et synchrone. L’analyse de l’EEG a montre la presence d’ondes lentes theta isolees ou des sequences d’ondes theta rythmiques (4–5 Hz) visibles au vertex, concomitantes des myoclonies. Le moyennage retrograde n’a montre aucune modification EEG precedant les myoclonies, par contre, il a revele un potentiel evoque par les myoclonies, compose de trois ondes consecutives predominant sur l’electrode Cz : N1, a 113 ms (± 6 ; 108–125), P2 a 202 ms (± 16 ; 180–228) et N2 a 350 ms (± 49, 260–400), amplitude de 23 μV (± 6 ; 12–28). Le moyennage des stimuli somato-sensitifs (obtenus par la percussion de la paume des mains et de la plante des pieds) chez 2 nouveau-nes presentant un MBSC et chez 2 temoins sains, a montre des reponses similaires et comparables a celles rapportees dans la litterature comme des potentiels evoques somesthesiques tardifs du nouveau-ne [1] , [2] , [3] . Nous avons demontre que les myoclonies dans le MBSC, evoquaient des PES tardifs predominant au vertex, realisant des ondes theta a 4–5 Hz, isolees ou en sequences repetitives, lors des clusters de myoclonies rythmiques. Cet aspect pourrait etre interprete comme critique et conduire a des traitements anti-epileptiques avec un risque de majoration des myoclonies.

Objective The recent discovery of the involvement of PCDH-19 gene in epilepsy in female with intellectual deficit and its cognitive consequences opened the research field in this area. Seizure types and EEG aspects are reported in a few series. However, neuropsychological and behavioural studies are not detailed. We aimed to better explore those aspects. Methods We assessed the intellectual, language, executive and emotional aspects with standardized psychometric tools in patients with PCDH-19. In addition, we proposed a detailed psychiatric evaluation and parental questionnaires. Results We included seven patients aged from 6 to 17 years. The analysis of cognitive profiles reveals scores ranging from 35 to 84 IQ points with a mental retardation in 6/7. Based on estimated ages, language and theory of mind are low for age. Those cognitive disabilities are associated with autism in 3/7 and non specified autism spectrum disorders in 3/7. One patient present an untypical profile with no MR or autistic features. Conclusion This study shows the negative impact of PCDH-19 mutation on cognitive behavioural and psychiatric development in addition to the burden of seizures. A specific follow-up and rehabilitation focusing on these aspects is recommanded.

Du fait de l’âge des patients et de pathologies specifiquement pediatriques, la pratique de l’EEG chez l’enfant, bien que repondant aux meme principes que chez l’adulte, requiert des competences specifiques pour l’enregistrement comme pour l’analyse des traces. Les adaptations techniques portent sur le nombre d’electrodes qui doit parfois etre diminue, les conditions d’enregistrement liees a des indications specifiques en reanimation et en neonatalogie, la necessite d’obtenir du sommeil chez le jeune enfant, la gestion des parents… L’interpretation doit prendre en compte une variabilite physiologique plus importante que chez l’adulte avec une evolution rapide de l’activite EEG en fonction de l’âge, y compris des aspects tres specifiques chez le nouveau-ne. Les indications sont assez superposables a celles rencontrees chez l’adulte mais une connaissance des formes pediatriques est necessaire. Cela s’applique a l’epilepsie avec les nombreux syndromes epileptiques de l’enfant, mais aussi a des situations d’urgence comme l’anoxie neonatale. Informations complementaires Au nom du groupe des recommandations coordonne par N. Obadia et P. Sauleau.

Introduction and Objectives: Few extensive studies have assessed the effects of botulinum neurotoxin A in adults with upper limb spasticity (ULS) poststroke/traumatic brain injury (TBI) on muscle tone, spasticity, active range of motion (AROM), and function. The aim of this study was to assess the efficacy and safety of abobotulinumtoxinA (Dysport) in hemiparetic adults with ULS poststroke/TBI. Methods: In this phase 3, prospective, double-blind, placebo-controlled study, 243 patients (34 sites, 9 countries) were randomly assigned (1:1:1) to Dysport 500 or 1000 U or placebo. The primary objective was assessment of upper limb muscle tone (Modified Ashworth Scale; MAS) in the primary targeted muscle group (PTMG; finger, wrist, or elbow flexors). Other measures included spasticity (Tardieu Scale), AROM, ease of applying splint (EOS), clinical benefit (Physician Global Assessment; PGA), and subjective function (Disability Assessment Scale; DAS). Results: Four weeks postinjection, a higher proportion of patients achieved a ≥1 point improvement in MAS with both Dysport doses compared with placebo (placebo, 22.8%; 500 U, 73.8%; 1000 U, 78.5%; P

Objective: To describe initial and follow-up electroencephalographic (EEG) characteristics in anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis. Methods: Consecutive polygraphic video-EEG recordings were analyzed in nine pediatric patients with anti-NMDAR encephalitis at the initial stage of the disease and during the intermediate period until motor recovery. EEG characteristics in waking and sleep stages as well as EEG correlates of abnormal movements are described. Results: In six patients, the waking EEG showed preserved background activity and either focal or unilateral hemispheric slowing. These children had more favorable outcome than the three children with diffuse slowing. Unilateral abnormal movements contra-lateral to hemispheric or focal slowing were also indicative of milder severity when compared to generalized abnormal movements and diffuse slowing. During non-rapid eye movement (NREM) sleep, a decrease in the expected slow waves and unilateral or diffuse theta–alpha band rhythms were observed in six children, not correlated with the outcome, representing a suggestive EEG pattern of anti-NMDAR encephalitis. Conclusions: In pediatric patients presenting behavioral disorders and abnormal movements, early EEG patterns may be suggestive of anti-NMDAR encephalitis. Moreover early electro-clinical presentation contributes to outcome prediction. Significance: This case series demonstrates that early EEG patterns may be suggestive of anti-NMDAR encephalitis in pediatric patients with behavioral disorders and abnormal movements.