Search

OBJECTIVE: Epilepsy is common in patients with PIGN diseases due to biallelic variants; however, limited epilepsy phenotyping data have been reported. We describe the epileptology of PIGN encephalopathy. METHODS: We recruited patients with epilepsy due to biallelic PIGN variants and obtained clinical data regarding age at seizure onset/offset and semiology, development, medical history, examination, electroencephalogram, neuroimaging, and treatment. Seizure and epilepsy types were classified. RESULTS: Twenty six patients (13 female) from 26 families were identified, with mean age 7 years (range = 1 month to 21 years; three deceased). Abnormal development at seizure onset was present in 25 of 26. Developmental outcome was most frequently profound (14/26) or severe (11/26). Patients presented with focal motor (12/26), unknown onset motor (5/26), focal impaired awareness (1/26), absence (2/26), myoclonic (2/26), myoclonic-atonic (1/26), and generalized tonic-clonic (2/26) seizures. Twenty of 26 were classified as developmental and epileptic encephalopathy (DEE): 55% (11/20) focal DEE, 30% (6/20) generalized DEE, and 15% (3/20) combined DEE. Six had intellectual disability and epilepsy (ID+E): two generalized and four focal epilepsy. Mean age at seizure onset was 13 months (birth to 10 years), with a lower mean onset in DEE (7 months) compared with ID+E (33 months). Patients with DEE had drug-resistant epilepsy, compared to 4/6 ID+E patients, who were seizure-free. Hyperkinetic movement disorder occurred in 13 of 26 patients. Twenty-seven of 34 variants were novel. Variants were truncating (n = 7), intronic and predicted to affect splicing (n = 7), and missense or inframe indels (n = 20, of which 11 were predicted to affect splicing). Seven variants were recurrent, including p.Leu311Trp in 10 unrelated patients, nine with generalized seizures, accounting for nine of the 11 patients in this cohort with generalized seizures. SIGNIFICANCE: PIGN encephalopathy is a complex autosomal recessive disorder associated with a wide spectrum of epilepsy phenotypes, typically with substantial profound to severe developmental impairment.

To develop an electrophysiological marker of proprioceptive spino-cortical tracts integrity based on corticokinematic coherence (CKC) in young children with unilateral cerebral palsy (UCP), in whom behavioral measures are not applicable.Electroencephalography (EEG) signals from 12 children with UCP aged 19 to 57 months were recorded using 128-channel EEG caps while their fingers were moved at 2 Hz by an experimenter, in separate sessions for the affected and non-affected hands. The coherence between movement kinematics and EEG signals (i.e., CKC) was computed at the sensor and source (using a realistic head model) levels. Peaks of CKC obtained for the affected and non-affected hands were compared for location and strength. The relation between CKC strength on the lesion-side, the lesion-type (cortico-subcortical vs. subcortical) and the level of manual ability were studied with 2-way repeated-measures ANOVA.At the individual level, a significant CKC peak at the central area contralateral to the moved hand was found in all young children with their non-affected hand and in 8 out of 12 children with their affected hand. At the group level, CKC to the affected hand movements was weaker than CKC to the non-affected hand movements. This difference was influenced by the type of lesion, the effect being predominant in the subgroup (n = 5) with cortico-subcortical lesions.CKC is measurable with EEG in young children with UCP and provides electrophysiological evidence for altered proprioceptive spino-cortical tracts on the lesioned brain hemisphere, particularly in children with cortico-subcortical lesions.

Since last 2 decades, High Frequency Oscillations (HFOs) are studied as a promising biomarker to localize the epileptogenic zone of patients with refractory focal epilepsy. As HFOs visual detection is time consuming and subjective, automatization of HFO detection is required. Most HFO detectors were developed on invasive electroencephalograms (iEEG) whereas scalp electroencephalograms (EEG) are used in clinical routine. In order HFO detection can benefit to more patients, scalp HFO detectors has to be developed. However, HFOs identification in scalp EEG is more challenging than in iEEG since scalp HFOs are of lower rate, lower amplitude and more likely to be corrupted by several sources of artifacts than iEEG HFOs. The main goal of this study is to explore the ability of deep learning architecture to identify scalp HFOs from the remaining EEG signal. Hence, a binary classification Convolutional Neural Network (CNN) is learned to analyze High Density Electroencephalograms (HD-EEG). EEG signals are first mapped into a 2D time-frequency image, several color definitions are then used as an input for the CNN. Experimental results show that deep learning allows simple end-to-end learning of preprocessing, feature extraction and classification modules while reaching competitive performance.

Synaptic inhibition is essential for shaping the dynamics of neuronal networks, and aberrant inhibition is linked to epilepsy. Gephyrin (Geph) is the principal scaffolding protein at inhibitory synapses and is essential for postsynaptic clustering of glycine (GlyRs) and GABA type A receptors. Consequently, gephyrin is crucial for maintaining the relationship between excitation and inhibition in normal brain function and mutations in the gephyrin gene (GPHN) are associated with neurodevelopmental disorders and epilepsy. We identified bi-allelic variants in the GPHN gene, namely the missense mutation c.1264G > A and splice acceptor variant c.1315-2A > G, in a patient with developmental and epileptic encephalopathy. We demonstrate that the splice acceptor variant leads to nonsense-mediated mRNA decay. Furthermore, the missense variant (D422N) alters gephyrin structure, as examined by analytical size exclusion chromatography and circular dichroism-spectroscopy, thus leading to reduced receptor clustering and sensitivity towards calpain-mediated cleavage. In addition, both alterations contribute to an observed reduction of inhibitory signal transmission in neurons, which likely contributes to the pathological encephalopathy.

International audience

No abstract available

Developmental and epileptic encephalopathies are conditions where there is developmental impairment related to both the underlying etiology independent of epileptiform activity and the epileptic encephalopathy. Usually they have multiple etiologies. Therefore, long-term outcome is related to both etiology-related factors and epilepsy-related factors-age at onset of epilepsy, type(s) of seizure(s), type of electroencephalographic abnormalities, duration of the epileptic disorder. This paper focuses on long-term outcome of six developmental and epileptic encephalopathies with onset from the neonatal period to childhood: early epileptic encephalopathy with suppression bursts, West syndrome, Dravet syndrome, Lennox-Gastaut syndrome, epilepsy with myoclonic atonic seizures and epileptic encephalopathy with continuous spike and waves during slow-wave sleep including Landau-Kleffner syndrome. For each syndrome, definition, main etiologies if multiple, and long-term outcome are discussed.

Plasticity of synaptic strength and density is a vital mechanism enabling memory consolidation, learning, and neurodevelopment. It is strongly dependent on the intact function of N-Methyl-d-Aspartate Receptors (NMDAR). The importance of NMDAR is further evident as their dysfunction is involved in many diseases such as schizophrenia, Alzheimer's disease, neurodevelopmental disorders, and epilepsies. Synaptic plasticity is thought to be reflected by changes of sleep slow wave slopes across the night, namely higher slopes after wakefulness at the beginning of sleep than after a night of sleep. Hence, a functional NMDAR deficiency should theoretically lead to altered overnight changes of slow wave slopes. Here we investigated whether pediatric patients with anti-NMDAR encephalitis, being a very rare but unique human model of NMDAR deficiency due to autoantibodies against receptor subunits, indeed show alterations in this sleep EEG marker for synaptic plasticity. We retrospectively analyzed 12 whole-night EEGs of 9 patients (age 4.3-20.8 years, 7 females) and compared them to a control group of 45 healthy individuals with the same age distribution. Slow wave slopes were calculated for the first and last hour of Non-Rapid Eye Movement (NREM) sleep (factor 'hour') for patients and controls (factor 'group'). There was a significant interaction between 'hour' and 'group' (p = 0.013), with patients showing a smaller overnight decrease of slow wave slopes than controls. Moreover, we found smaller slopes during the first hour in patients (p = 0.022), whereas there was no group difference during the last hour of NREM sleep (p = 0.980). Importantly, the distribution of sleep stages was not different between the groups, and in our main analyses of patients without severe disturbance of sleep architecture, neither was the incidence of slow waves. These possible confounders could therefore not account for the differences in the slow wave slope values, which we also saw in the analysis of the whole sample of EEGs. These results suggest that quantitative EEG analysis of slow wave characteristics may reveal impaired synaptic plasticity in patients with anti-NMDAR encephalitis, a human model of functional NMDAR deficiency. Thus, in the future, the changes of sleep slow wave slopes may contribute to the development of electrophysiological biomarkers of functional NMDAR deficiency and synaptic plasticity in general.

Background: Primary microcephaly (PM) is defined as a significant reduction in occipitofrontal circumference (OFC) of prenatal onset. Clinical and genetic heterogeneity of PM represents a diagnostic challenge. Methods: We performed detailed phenotypic and genomic analyses in a large cohort (n = 169) of patients referred for PM and could establish a molecular diagnosis in 38 patients. Results: Pathogenic variants in ASPM and WDR62 were the most frequent causes in non-consanguineous patients in our cohort. In consanguineous patients, microarray and targeted gene panel analyses reached a diagnostic yield of 67%, which contrasts with a much lower rate in non-consanguineous patients (9%). Our series includes 11 novel pathogenic variants and we identify novel candidate genes including IGF2BP3 and DNAH2. We confirm the progression of microcephaly over time in affected children. Epilepsy was an important associated feature in our PM cohort, affecting 34% of patients with a molecular confirmation of the PM diagnosis, with various degrees of severity and seizure types. Conclusion: Our findings will help to prioritize genomic investigations, accelerate molecular diagnoses, and improve the management of PM patients., SCOPUS: ar.j, info:eu-repo/semantics/published

Objectives To describe neurological characteristics and CNS involvement on MRI in secondary hemophagocytic lymphohistiocytosis (sHLH) and differentiate it from primary hemophagocytic lymphohistiocytosis (pHLH) and acute disseminated encephalomyelitis (ADEM). Methods Nine children with sHLH who had neurological symptoms were retrospectively included. Characteristics of brain MRI were compared to those of 15 children with pHLH and neurological involvement and 44 children with ADEM. Results Three children (33%) presented with isolated neurological symptoms. Neurological signs occurred within one month following Epstein-Barr virus primary infection or systemic juvenile arthritis exacerbation in 8 patients (89%). Eight children (89%) had MRI lesions. sHLH MRI lesions were distinct of those of pHLH by morphology and signal with more frequent hyposignal intensities on T1-weighted sequences (p = 0.01) and well-defined and less fuzzy lesions (p = 0.03). All patients survived and one patient presented severe motor and cognitive disability. Conclusion Neurological symptoms of sHLH are non-specific and their outcome is favorable in most of the children. MRI at onset may help to differentiate this condition from pHLH.

International audience; CACNA1A pathogenic mutations are involved in various neurological phenotypes including episodic ataxia (EA2), spinocerebellar ataxia (SCA6), and familial hemiplegic migraine (FHM1). Epilepsy is poorly documented. We studied 18 patients (10 males) carrying de novo or inherited CACNA1A mutations, with median age of 2,5 years at epilepsy onset. Eight mutations were novel. Two variants known leading to gain of function (GOF) were found in 5 patients. Five other patients had non-sense variants leading to loss of function (LOF). Seizures were most often revealed by either status epilepticus (SE) (n = 8), eventually triggered by fever (n = 5), or absences/behavioural arrests (n = 7). Non-epileptic paroxysmal events were frequent and consisted in recurrent hemiplegic accesses (n = 9), jitteriness in the neonatal period (n = 6), and ocular paroxysmal events (n = 9). Most of the patients had early permanent cerebellar dysfunction (n = 16) and early moderate to severe global developmental delay (GDD)/intellectual deficiency (ID) (n = 17). MRI was often abnormal, with cerebellar (n = 8) and/or cerebral (n = 6) atrophy. Stroke-like occurred in 2 cases. Some antiepileptic drugs including topiramate, levetiracetam, lamotrigine and valproate were effective on seizures. Acetazolamide and calcium channel blockers were often effective when used. More than half of the patients had refractory epilepsy. CACNA1A mutation should be evoked in front of 2 main electro-clinical phenotypes that are associated with permanent cerebellar dysfunction and moderate to severe GDD/ID. The first one, found in all 5 patients with GOF variants, is characterized by intractable seizures, early and recurrent SE and hemiplegic accesses. The second, less severe, found in 5 patients with LOF variants, is characterized by refractory early onset absence seizures.

Primary microcephaly (PM) is defined as a significant reduction in occipito-frontal circumference (OFC) of prenatal onset. Clinical and genetic heterogeneity of PM represents a diagnostic challenge. We performed detailed phenotypic and genomic analyses in a large cohort (n=169) of patients referred for PM, and could establish a molecular diagnosis in 38 patients. Pathogenic variants in ASPM and WDR62 were the most frequent causes in non-consanguineous patients in our cohort. In consanguineous patients, microarray and targeted gene panel analyses reached a diagnostic yield of 67%, which contrasts with a much lower rate in outbred patients (9%). Our series includes 15 previously unreported families and 11 novel pathogenic variants, and we identify novel candidate genes including IGF2BP3, DNAH2, and TSR1. We confirm progression of microcephaly over time in affected children. Epilepsy was an important associated feature in our PM cohort, affecting 34% of patients, with various degrees of severity and seizure types. Our findings will help to prioritize genomic investigations, accelerate molecular diagnoses and improve management of PM patients.

International audience; Purpose:CACNA1C encodes the alpha-1-subunit of a voltage-dependent L-type calcium channel expressed in human heart and brain. Heterozygous variants in CACNA1C have previously been reported in association with Timothy syndrome and long QT syndrome. Several case reports have suggested that CACNA1C variation may also be associated with a primarily neurological phenotype.Methods:We describe 25 individuals from 22 families with heterozygous variants in CACNA1C, who present with predominantly neurological manifestations.Results:Fourteen individuals have de novo, nontruncating variants and present variably with developmental delays, intellectual disability, autism, hypotonia, ataxia, and epilepsy. Functional studies of a subgroup of missense variants via patch clamp experiments demonstrated differential effects on channel function in vitro, including loss of function (p.Leu1408Val), neutral effect (p.Leu614Arg), and gain of function (p.Leu657Phe, p.Leu614Pro). The remaining 11 individuals from eight families have truncating variants in CACNA1C. The majority of these individuals have expressive language deficits, and half have autism.Conclusion:We expand the phenotype associated with CACNA1C variants to include neurodevelopmental abnormalities and epilepsy, in the absence of classic features of Timothy syndrome or long QT syndrome.

Plasticity of synaptic strength and density is a vital mechanism enabling memory consolidation, learning, and neurodevelopment. It is strongly dependent on the intact function of N-methyl-D-aspartate receptors (NMDAR). The importance of NMDAR is further evident as their dysfunction is involved in many diseases such as schizophrenia, Alzheimer’s disease, neurodevelopmental disorders, and epilepsies. Synaptic plasticity is thought to be reflected by changes of sleep slow wave slopes across the night, namely higher slopes after wakefulness at the beginning of sleep than after a night of sleep. Hence, a functional NMDAR deficiency should theoretically lead to altered overnight changes of slow wave slopes. Here we investigated whether pediatric patients with anti-NMDAR encephalitis, being a very rare but unique human model of NMDAR deficiency due to autoantibodies against receptor subunits, indeed show alterations in this sleep EEG marker for synaptic plasticity.We retrospectively analyzed 12 whole-night EEGs of 9 patients (age 4.3-20.8 years, 7 females) and compared them to a control group of 45 healthy individuals with the same age distribution. Slow wave slopes were calculated for the first and last hour of non-rapid eye movement (NREM) sleep (factor ‘hour’) for patients and controls (factor ‘group’). There was a significant interaction between ‘hour’ and ‘group’ (p = 0.013), with patients showing a smaller overnight decrease of slow wave slopes than controls. Moreover, we found smaller slopes during the first hour in patients (p = 0.022), whereas there was no group difference during the last hour of NREM sleep (p = 0.980). Importantly, the distribution of sleep stages was not different between the groups, and in our main analyses of patients without severe disturbance of sleep architecture, neither was the incidence of slow waves. These possible confounders could therefore not account for the differences in the slow wave slope values, which we also saw in the analysis of the whole sample of EEGs.These results suggest that quantitative EEG analysis of slow wave characteristics may reveal impaired synaptic plasticity in patients with anti-NMDAR encephalitis, a human model of functional NMDAR deficiency. Thus, in the future, the changes of sleep slow wave slopes may contribute to the development of electrophysiological biomarkers of functional NMDAR deficiency and synaptic plasticity in general.HighlightsChanges of slow waves in overnight EEGs are thought to reflect synaptic plasticity.Synaptic plasticity is strongly dependent on intact NMDAR function.Antibody-mediated NMDAR deficiency occurs in patients with anti-NMDAR encephalitis.In this human model of NMDAR deficiency, we found altered slow wave changes.Sleep EEG measures may mark NMDAR-related impairments of synaptic plasticity.

Purpose To determine whether awake EEG criteria can differentiate epileptic encephalopathy with continuous spike and waves during sleep (EE-CSWS) at the time of cognitive regression from typical, self-limited focal epilepsy (SFE). Methods This retrospective case-control study was based on the analysis of awake EEGs and included 15 patients with EE-CSWS and 15 age-matched and sex-matched patients with typical SFE. The EEGs were anonymised and scored by four independent readers. The following qualitative and quantitative EEG indices were analysed: slow-wave index (SLWI), spike-wave index (SWI), spike-wave frequency (SWF), long spike-wave clusters (CLSW) and EEG score (between grades 0 and 4). Sensitivity and specificity were assessed using receiver operating characteristic (ROC) curves and their reproducibility with a kappa test. Results Based on a highly sensitive cut-off, EE-CSWS patients were 8.4 times more likely than those with SFE to have an SLWI > 6%, 15 times more likely to have an SWI > 10 % and six times more likely to have a CLSW of ≥ 1 s. There was substantial agreement between readers (with kappa values of 0.64, 0.69 and 0.67). EE-CSWS patients were 13 times more likely to have an SWF of > 11 % and 149 times more likely to have an EEG score of ≥ 3 than typical SFE patients. Agreement about these ratings was almost perfect (kappa 0.91 and 0.86). Conclusion An EEG score of ≥ 3 on a 20-min awake EEG differentiates typical SFE from EE-CSWS at the time of cognitive regression, with good reliability across readers with different levels of expertise.

Epileptic encephalopathy with continuous spike and waves during slow-wave sleep (CSWS) is a spectrum of epileptic conditions best defined by the association of cognitive or behavioral impairment acquired during childhood and not related to another factor than the presence of abundant interictal epileptiform discharges (IEDs) during sleep, which tend to diffuse over the whole scalp. It is part of the childhood focal epileptic syndromes. Some cases are genetic, related to GRIN2A mutation that impairs the glutamate NMDA receptor functions, and overlap with benign epilepsy with central temporal spikes. Others are related to a structural brain lesion that may affect either the cortex or the thalami. Most cases are of unknown etiology. Landau-Kleffner syndrome (LKS) is a particular presentation where acquired aphasia is the core symptom. Clinical, neurophysiological, and cerebral glucose metabolism data support the hypothesis that IEDs play a prominent role in the cognitive deficits by interfering with the neuronal networks at the site of the epileptic foci but also at distant connected areas. Therefore, the treatment should aim to suppress CSWS. This may be achieved using conventional antiepileptic drugs, but corticosteroids seem to have more pronounced and sustained efficacy. Outcome for epilepsy is usually good, CSWS being an age-dependent EEG pattern, whereas outcome for cognition, language, and behavior is variable. Rehabilitation represents an important part of the treatment, and visual forms of language should be encouraged in children with LKS.

Study question Is assisted conception associated with neonatal morbidity and mortality and with neurodevelopmental impairment at 2 years of corrected age in preterm infants born before 34 weeks of gestational age? Summary answer Assisted conception is not associated with an increase in neonatal morbidity and mortality and is even significantly associated with a better 2-year neurodevelopmental outcome in preterm infants. What is known already Assisted conception appears to increase the rate of preterm births, though few studies have analysed outcomes for these preterm infants. Study design, size, duration This prospective observational study included 703 preterm infants born between January 2009 and December 2013 and 573 of them were assessed at 2 years of corrected age. Participants/materials, setting, methods All infants born alive between 24+0 and 33+6 weeks of gestational age and hospitalised at the Angers University Hospital were eligible as long as the mode of conception was known for neonatal outcome assessment. They were enroled in the Loire Infant Follow-up Team (LIFT) prospective longitudinal cohort and included for neurodevelopmental outcome assessment. Neonatal morbidity and mortality were evaluated during hospitalisation based on a composite score including death, intraventricular haemorrhage Grade ≥3, periventricular leukomalacia, treated patent ductus arteriosus and bronchopulmonary dysplasia at 36 weeks of gestational age. The neurodevelopmental outcome at 2 years of corrected age was determined by a physical examination, a neuropsychological test and a parental questionnaire. In order to ensure comparability, infants were matched 1:1 according to maternal age, twin status and propensity score,calculated from variables usually associated (positively or negatively) with assisted conception, including gestational age, z-score of birth weight, antenatal corticosteroids and magnesium sulphate treatments, gender, parity, maternal body mass index, tobacco consumption, outborn delivery (i.e. not at a tertiary-care medical centre) and maternal socio-economic status. Main results and the role of chance There were 703 preterm infants included in the analysis of neonatal morbidity and mortality, including 137 born after assisted conception. After matching, 184 preterm infants were included for neonatal morbidity and mortality analysis. There was no significant association between assisted conception and neonatal morbidity and mortality (aOR 0.67, 95% CI [0.25, 1.77], P = 0.422). 573 infants were assessed at 2 years, including 121 born after assisted conception. After matching, 154 preterm infants were included for neurodevelopmental outcome analysis. Assisted conception was significantly associated with a reduction in the probability of non-optimal neurological development at 2 years (aOR 0.26, 95% CI [0.09, 0.80], P = 0.019). Limitation, reasons for caution Further studies remain necessary to fully confirm these results. This was a monocentric study and 14% of enroled infants were lost to follow up at 2 years of corrected age. Wider implications of the findings These findings are relevant for providing appropriate information to parents considering assisted conception, and more importantly for those with a preterm infant following a pregnancy achieved by assisted conception. Study funding/competing interest(s) The authors report external funding and no conflicts of interest for this work. Trial registration number N/A.

International audience; Objective Maternal obesity is associated with an increase in maternal, foetal and neonatal morbidity and mortality. The aim of our study was to evaluate the relationships between maternal pre-pregnancy body mass index and (1) neonatal outcome in preterm infants, and (2) neurodevelopmental outcome at 2 years of corrected age. Method We conducted a single-centre cohort study. Infants born between 24+0 and 33+6 weeks of gestation between January 2009 and December 2013, hospitalised in the neonatal intensive care unit of Angers University Hospital, and with available data regarding maternal pre-pregnancy body mass index were eligible. Three groups were defined according to maternal body mass index: normal (n = 418), overweight (n = 136) and obese (n = 89). The primary outcome was neurodevelopment at 2 years of corrected age. Children with a non-optimal neuromotor and/or psychomotor assessment and/or a sensory disability were regarded as having a “non-optimal neurodevelopmental outcome”. Neuromotor function was regarded as non-optimal when cerebral palsy was present or when the clinical examination revealed neurological signs of abnormal muscular tone. Psychomotor assessment was regarded as non-optimal if the revised Brunet-Lézine test was < 85 or when the overall score in the parental Ages and Stages Questionnaire (ASQ) was < 185. Finally, sensory disabilities such as blindness and children who required a hearing aid were taken into account. The secondary outcome was the composite criteria of neonatal complications. Multivariable analysis included the following variables: mother’s age, gestational age, smoking during pregnancy, magnesium sulphate and steroid treatment during pregnancy, twin status, gender, socioeconomic status and social security benefits for those with low incomes. Results The study population was composed of 643 preterm infants. Among them, 520 were assessed at 2 years. There was no difference in the proportion of infants with non-optimal neurodevelopmental outcomes between the three groups (16.6% for obese, 13.5% for overweight, 16.9% for normal body mass index mothers; p = 0.73). According to multivariable analysis, being born from an overweight or obese mother was not associated with an increased risk of non-optimal neuro-development at 2 years (adjusted OR = 0.84 [0.40–1.76] for obese, adjusted OR = 0.83 [0.43–1.59] for overweight mothers). There was no difference in the proportion of preterm infants with a non-optimal composite criterion of neonatal complications between the three groups. In the multivariable analysis, being born from an overweight or obese mother was not associated with an increased risk of non-optimal neonatal outcomes (adjusted OR = 0.95 [0.49–1.83] for obese, adjusted OR = 1.18 [0.69–2.01] for overweight mothers). Conclusion In this large prospective cohort of preterm infants born before 34 weeks of gestation, we found no relationship between maternal body mass index and neurodevelopmental outcomes at 2 years of corrected age and no relationship between maternal body mass index and neonatal outcomes. Other prematurity-related factors may be more relevant for neurodevelopmental outcome than the mother’s pre-pregnancy BMI.

Objective: Our goal is to use existing and to propose new time–frequency entropy measures that objectively evaluate the improvement on epileptic patients after medication by studying their resting state electroencephalography (EEG) recordings. An increase in the complexity of the signals would confirm an improvement in the general state of the patient. Methods: We review the Renyi entropy based on time–frequency representations, along with its time-varying version. We also discuss the entropy based on singular value decomposition computed from a time–frequency representation, and introduce its corresponding time-dependant version. We test these quantities on synthetic data. Friedman tests are used to confirm the differences between signals (before and after proper medication). Principal component analysis is used for dimensional reduction prior to a simple threshold discrimination. Results: Experimental results show a consistent increase in complexity measures in the different regions of the brain. These findings suggest that extracted features can be used to monitor treatment. When combined, they are useful for classification purposes, with areas under ROC curves higher than 0.93 in some regions. Conclusion: Here we applied time–frequency complexity measures to resting state EEG signals from epileptic patients for the first time. We also introduced a new time-varying complexity measure. We showed that these features are able to evaluate the treatment of the patient, and to perform classification. Significance: The time–frequency complexities, and their time-varying versions, can be used to monitor the treatment of epileptic patients. They could be applied to a wider range of problems.

International audience; In epilepsy syndromes of childhood with sleep activation, defined as the spectrum of epileptic conditions going from classical benign childhood epilepsy with centrotemporal spikes (BECTS) to epileptic encephalopathy (EE) with continuous spike and waves during slow-wave sleep (CSWS) including Landau-Kleffner syndrome (LKS), a lot of functional imaging studies have been performed so far, leading to results that are not always consistent, related to the technique of neuroimaging performed and to the variability of the clinical phenotype. Most consistent findings are, depending of the method used, activations or increased regional glucose metabolism in the epileptogenic regions, and deactivations, hypometabolism or decreased functional connectivity in cortical regions that belong to the default mode network. Functional changes are either transitory, temporally related to the occurrence of interictal epileptiform discharges (IED), or permanent, persisting across IED-free periods. Some studies have shown that the more severe phenotype, i.e. EE with CSWS, displays the more profound functional disturbances. Taken together, functional imaging studies support the concept that IED impact cognition in epilepsy syndromes of childhood with sleep activation. However, the precise chronology between the occurrence of IED and the functional disturbances, the neuropsychological correlates of the functional disturbances, and the effects of the anti-epileptic treatments on IED, functional disturbances and cognition need to be further studied.Copyright © 2019 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

We propose new multichannel time-frequency complexity measures to evaluate differences on magnetoencephalograpy (MEG) recordings between healthy young and old subjects at rest at different spatial scales. After reviewing the Renyi and singular value decomposition entropies based on time-frequency representations, we introduce multichannel generalizations, using multilinear singular value decomposition for one of them. We test these quantities on synthetic data, illustrating how the introduced complexity measures focus on number of components, nonstationarity and similarity across channels. Friedman tests are used to confirm the differences between young and old groups, and heterogeneity within groups. Experimental results show a consistent increase in complexity measures for the old group. When analyzing the topographical distribution of complexity values, we found clusters in the frontal sensors. The complexity measures here introduced seem to be a better indicator of the neurophysiologic changes of aging than power envelope connectivity. Here we applied new multichannel time-frequency complexity measures to resting-state MEG recordings from healthy young and old subjects. We showed that these features are able to reveal regional clusters. The multichannel time-frequency complexities can be used to monitor the aging of subjects. They also allow a mutual information approach, and could be applied to a wider range of problems. Fil: Colominas, Marcelo Alejandro. Universidad Nacional de Entre Ríos. Instituto de Investigación y Desarrollo en Bioingeniería y Bioinformática - Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Investigación y Desarrollo en Bioingeniería y Bioinformática; Argentina Fil: Wens, Vincent. Laboratoire de Cartographie Fonctionnelle Du Cerveau; Bélgica Fil: Mary, Alison. Universite de Normandie; Francia Fil: Coquelet, Nicolas. Laboratoire de Cartographie Fonctionnelle Du Cerveau; Bélgica Fil: El Sayed Hussein Jomaa, Mohamad. Laboratoire Angevin de Recherche En Ingénierie Des Syst; Francia Fil: Jrad, Nisrine. Laboratoire Angevin de Recherche En Ingénierie Des Syst; Francia Fil: Humeau-Heurtier, Anne. Laboratoire Angevin de Recherche En Ingénierie Des Syst; Francia Fil: Van Bogaert, Patrick. Centre Hospitalier Universitaire Angers; Francia

International audience; Epilepsy of infancy with migrating focal seizures was first described in 1995. Fifteen years later, KCNT1 gene mutations were identified as the major disease-causing gene of this disease. Currently, the data on epilepsy of infancy with migrating focal seizures associated with KCNT1 mutations are heterogeneous and many questions remain unanswered including the prognosis and the long-term outcome especially regarding epilepsy, neurological and developmental status and the presence of microcephaly. The aim of this study was to assess data from patients with epilepsy in infancy with migrating focal seizures with KCNT1 mutations to refine the phenotype spectrum and the outcome. We used mind maps based on medical reports of children followed in the network of the French reference centre for rare epilepsies and we developed family surveys to assess the long-term outcome. Seventeen patients were included [age median (25th-75th percentile) 4 (2-15) years, sex ratio 1.4, length of follow-up 4 (2-15) years]. Seventy-one per cent started at 6 (1-52) days with sporadic motor seizures (n = 12), increasing up to a stormy phase with long lasting migrating seizures at 57 (30-89) days. The others entered this stormy phase directly at 1 (1-23) day. Ten patients entered a consecutive phase at 1.3 (1-2.8) years where seizures persisted at least daily (n = 8), but presented different semiology brief and hypertonic with a nocturnal (n = 6) and clustered (n = 6) aspects. Suppression interictal patterns were identified on the EEG in 71% of patients (n = 12) sometimes from the first EEG (n = 6). Three patients received quinidine without reported efficacy. Long-term outcome was poor with neurological sequelae and active epilepsy except for one patient who had an early and long-lasting seizure-free period. Extracerebral symptoms probably linked with KCNT1 mutation were present, including arteriovenous fistula, dilated cardiomyopathy and precocious puberty. Eight patients (47%) had died at 3 (1.5-15.4) years including three from suspected sudden unexpected death in epilepsy. Refining the electro-clinical characteristics and the temporal sequence of epilepsy in infancy with migrating focal seizures should help diagnosis of this epilepsy. A better knowledge of the outcome allows one to advise families and to define the appropriate follow-up and therapies. Extracerebral involvement should be investigated, in particular the cardiac system, as it may be involved in the high prevalence of sudden unexpected death in epilepsy in these cases.

International audience; Cerebral palsy (CP), an umbrella term for a developmental motor disorder caused by early brain injury (EBI)/interference, remains debated. In this essay, we present a narrative, beginning with the original anatomical-clinical description of the so-called paralysie congéniale (congenial paralysis) by the French psychiatrist Jean-Baptiste Cazauvieilh. We then discuss how the concept has evolved over the last 2 centuries. We aim to illustrate these ideas with the biopsychosocial model of health, especially in light of the current neuroscientific and sociological knowledge of human development. We endeavour to integrate 3 connected but distinct entities: (1) the EBI as a seminal turning point of the individual's story; (2) the clinical findings we call CP, when motor impairment and activity limitation related to post-EBI (or other early non-progressive brain interference) appears, and; (3) a post-EBI developmental condition that encompasses the overall consequences of an EBI. This framework should guide individual, familial and collective care discussions and research strategies beyond the scope of CP.Copyright © 2019 Elsevier Masson SAS. All rights reserved.

Functional Connectivity (FC) is a powerful tool to investigate brain networks both in rest and while performing tasks. Functional magnetic resonance imaging (fMRI) gave good spatial estimation of FC but lacked the temporal resolution. Electroencephalography (EEG) allows estimating FC with good temporal resolution. In this study we introduce a new method based on Mutual Information and Multivariate Improved Weighted Multi-scale Permutation Entropy to estimate FC of brain using EEG. We applied this method on resting-state EEG signals from healthy children. Using network measures of nodes and Wilcoxon signed-rank test, we identified the most important nodes in the estimated networks. Comparing the localization of those outstanding nodes with the regions involved in resting-state networks (RSNs) estimated from fMRI showed that our proposal is efficient in the identification of nodes belonging to RSNs and could be used as a general estimator for FC without having to band-pass the signals into frequency bands.

International audience; Various specific early rehabilitation strategies are proposed to decrease functional disabilities in patients with cerebral palsy (CP). These strategies are thought to favour the mechanisms of brain plasticity that take place after brain injury. However, the level of evidence is low. Markers of brain plasticity would favour validation of these rehabilitation programs. In this paper, we consider the study of mu rhythm for this goal by describing the characteristics of mu rhythm in adults and children with typical development, then review the current literature on mu rhythm in CP. Mu rhythm is composed of brain oscillations recorded by electroencephalography (EEG) or magnetoencephalography (MEG) over the sensorimotor areas. The oscillations are characterized by their frequency, topography and modulation. Frequency ranges within the alpha band (∼10 Hz, mu alpha) or beta band (∼20 Hz, mu beta). Source location analyses suggest that mu alpha reflects somatosensory functions, whereas mu beta reflects motor functions. Event-related desynchronisation (ERD) followed by event-related (re-)synchronisation (ERS) of mu rhythm occur in association with a movement or somatosensory input. Even if the functional role of the different mu rhythm components remains incompletely understood, their maturational trajectory is well described. Increasing age from infancy to adolescence is associated with increasing ERD as well as increasing ERS. A few studies characterised mu rhythm in adolescents with spastic CP and showed atypical patterns of modulation in most of them. The most frequent findings in patients with unilateral CP are decreased ERD and decreased ERS over the central electrodes, but atypical topography may also be found. The patterns of modulations are more variable in bilateral CP. Data in infants and young children with CP are lacking and studies did not address the questions of intra-individual reliability of mu rhythm modulations in patients with CP nor their modification after motor learning. Better characterization of mu rhythm in CP, especially in infants and young children, is warranted before considering this rhythm as a potential neurophysiological marker of brain plasticity.