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Objective: The study aimed to address the challenge of early assessment of neonatal hypoxic-ischemic encephalopathy (HIE) severity to identify candidates for therapeutic hypothermia (TH). The objective was to develop an automated classification model for neonatal EEGs, enabling accurate HIE severity assessment 24/7., Methods: EEGs recorded within 6 h of life after perinatal anoxia were visually graded into 3 severity groups (HIE French Classification) and quantified using 6 qEEG markers measuring amplitude, continuity and frequency content. Machine learning models were developed on a dataset of 90 EEGs and validated on an independent dataset of 60 EEGs., Results: The selected model achieved an overall accuracy of 80.6% in the development phase and 80% in the validation phase. Notably, the model accurately identified 28 out of 30 children for whom TH was indicated after visual EEG analysis, with only 2 cases (moderate EEG abnormalities) not recommended for cooling., Conclusions: The combination of clinically relevant qEEG markers led to the development of an effective automated EEG classification model, particularly suited for the post-anoxic latency phase. This model successfully discriminated neonates requiring TH., Significance: The proposed model has potential as a bedside clinical decision support tool for TH., (Copyright © 2024 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Background: Attention-deficit hyperactivity disorder (ADHD) is a frequent comorbidity in children with epilepsy, which management mostly relies on the usual treatments of ADHD, especially methylphenidate. Supplementation with polyunsaturated n-3 Fatty Acid (PUFA) has been proposed as an alternative therapeutic approach in ADHD without epilepsy but has never been evaluated in epilepsy-associated ADHD., Methods: A multicenter double blind randomized placebo-controlled trial evaluating supplementation with PUFA, in eicosapentaenoic- and docosahexaenoic-acid form, conjugated to a phospholipid vector (PS-Omega3) in children aged >6 and <16-years old, and suffering from any type of epilepsy and ADHD (inattentive or combined type) according to DSM-V. After a 4-week baseline period, patients were allocated (1:1) either to placebo group or to PS-Omega 3 group and entered a 12 week-double-blind treatment period which was followed by a 12 week-open-label treatment period. The primary outcome was the reduction of the ADHD-rating scale IV attention-deficit subscore after 12 weeks of treatment., Results: The study was stopped early because of lack of eligible participants and the expected sample size was not reached. Seventy-four patients were randomized, 44 in PS-Omega3, and 30 in the placebo group. The reduction after 12 weeks of treatment in the inattention subscore of the ADHD-IV scale was -1.57 in the PS-Omega3 group, and -2.90 in the placebo group (p = 0.33, α = 5%). Results were similar after 24 weeks of treatment and for all other ADHD-related secondary outcomes, with no difference between placebo and PS-Omega3., Conclusion: Our study remaining underpowered, no formal conclusion about the effect of Ps-Omega3 could be drawn. However, our data strongly suggested that the PS-Omega 3 formulation used in the current study did not improve ADHD symptoms in children with epilepsy., Plain Language Summary: Supplementation with polyunsaturated n-3 Fatty Acid (PUFA) has been proposed in ADHD but has never been evaluated in patients with both epilepsy and ADHD. To address this issue, we conducted a multicenter double blind randomized placebo-controlled trial evaluating supplementation with PUFA in children with epilepsy and ADHD. The study was stopped early because of lack of eligible participants, hampering formal conclusion. However, the evolution of the ADHD symptoms at 12 and 24 weeks did not differ between placebo and PUFA supplementation, strongly suggesting that PUFA did not improve ADHD symptoms in children with epilepsy., (© 2024 The Authors. Epilepsia Open published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)

Perinatal anoxia remains an important public health problem as it can lead to hypoxic-ischaemic encephalopathy (HIE) and cause significant neonatal mortality and morbidity. The mechanisms of the fetal brain's response to hypoxia are still unclear and current methods of in utero HIE prediction are not reliable. In this study, we directly analysed the brain response to hypoxia in fetal sheep using in utero EEG. Near-term fetal sheep were subjected to progressive hypoxia induced by repeated umbilical cord occlusions (UCO) at increasing frequency. EEG changes during and between UCO were analysed visually and quantitatively, and related with gasometric and haemodynamic data. EEG signal was suppressed during occlusions and progressively slowed between occlusions with the increasing severity of the occlusions. Per-occlusion EEG suppression correlated with per-occlusion bradycardia and increased blood pressure, whereas EEG slowing and amplitude decreases correlated with arterial hypotension and respiratory acidosis. The suppression of the EEG signal during cord occlusion, in parallel with cardiovascular adaptation could correspond to a rapid cerebral adaptation mechanism that may have a neuroprotective role. The progressive alteration of the signal with the severity of the occlusions would rather reflect the cerebral hypoperfusion due to the failure of the cardiovascular adaptation mechanisms., (© 2023. The Author(s).)

Objectives: According to the WHO, more than 50 million people have epilepsy. Among them, nearly 80% of patients with epilepsy live in developing countries and 75% of them do not have access to treatment. The ketogenic diet (KD) has been shown as an effective alternative for patients with drug-resistant epilepsy. Although it has been studied in Asia, no such studies have been conducted in Vietnam. The purpose of this study was to verify the feasibility and tolerability of KD in children with refractory epilepsies in Vietnam., Methods: Children with drug-resistant epilepsy followed at Children's Hospital, Vietnam treated by KD were included in a prospective study from June 2019 to October 2021. Side-effects, retention rate, number, and duration of seizures were recorded after 1, 3, 6, 9 and 12 months of KD. Patients were considered as respondents when a 50% seizure frequency was reached. Tolerance and acceptability of the KD were closely monitored., Results: Forty-six children were included but KD was contraindicated for one patient. Due to the COVID pandemic, we had to rely on internet exchanges to stay in touch with families. Meals had to be adapted to Vietnamese culinary habits. The retention rate decreased from 82.2% at 1 month to 40% at 12 months of follow-up. The incidence of side effects was 44.4% and occurred mainly during the first month. Fifteen patients out of 45 were considered as responders after 12 months., Significance: Our study was the first attempt to introduce KD in Vietnam. It demonstrated that this diet was feasible and well tolerated. The KD diet resulted in significant improvement for 30% of our patients with drug-resistant epilepsy. This percentage is lower than in some studies but warrants the use of KD as a valuable alternative in a country where many patients lack access to recent treatments., (© 2023 The Authors. Epilepsia Open published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)

Introduction: Myotonic dystrophy type 1 (DM1) is associated with motor dysfunction as well as psychological and cognitive impairments, including altered social cognition. Theory of mind (ToM) impairments have been reported in this disease but their nature and their cognitive/cerebral correlates have yet to be determined., Methods: Fifty DM1 patients and 50 healthy controls were assessed using the Movie for the Assessment of Social Cognition, which quantifies impairments in affective and cognitive components of ToM through the depiction of everyday situations. We also measured the study participants' cognitive, behavioral and social abilities, quality of life, and brain MRI characteristics., Results: DM1 patients presented a significant impairment in ToM performance compared to controls (p < .001). The patients' errors were related to hypomentalizations (p < .001 vs controls) but not to hypermentalizations (p = .95). The affective component was affected (p < .001 vs controls) but not the cognitive component (p = .09). The ToM impairment was associated with demographic variables (older age and a lower educational level), genetic findings (a larger CTG triplets repeat expansion) and cognitive scores (slower information processing speed). Associations were also found with brain MRI variables (lower white matter and supratentorial volumes) but not with behavioral or social variables., Discussion: DM1 patients display a ToM impairment, characterized by predominant hypomentalizations concerning the affective component. This impairment might result from structural brain abnormalities observed in DM1., Competing Interests: Declaration of competing interest The authors have no disclosures to report., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Introduction: Various neurologic manifestations have already been described in children during or after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. The central nervous system disorders reported in children are mainly encephalopathies during multisystem inflammatory syndrome. We present here an acute meningoencephalitis with cerebral vasculitis associated to a coronavirus disease 2019 (COVID-19) infection in a 13-year-old girl with a 1-year clinical, electroencephalogram (EEG), and magnetic resonance imaging (MRI) follow-up., Case Report: A 13-year-old girl presented acute symptoms of consciousness impairment, frontal headache, hyperthermia, and aphasia, with moderate lymphopenia (900/mm 3 ), elevated C-reactive protein (17 mg/L), cerebrospinal fluid (CSF) pleocytosis (15 cells/mm 3 ), slow background with frontal focalization on EEG, a left frontal ischemic lesion, leptomeningeal enhancement, and bilateral limbic fluid-attenuated inversion recovery hyperintensity on cerebral MRI. Reverse transcription-polymerase chain reaction for SARS-CoV-2 was positive in nasopharyngeal swab and COVID serology was positive for immunoglobulin (Ig) M and G, whereas extensive autoimmune antibody investigation was negative except for a positive low titer of anti-myelin oligodendrocyte glycoprotein in CSF and blood. The diagnosis of probable encephalitis associated to cerebral vasculitis after COVID infection was suggested and steroids pulse were started. She recovered within a few days. Six months later, she had moderate clinical sequels including persistent intermittent headaches, an isolated spatial deficit, and focal spikes on the EEG without argument for epilepsia., Conclusion: A teenager without previous medical history presented with acute encephalitis with leptomeningitis and vasculitis after a recent COVID-19 infection. Steroids pulse therapy allowed clinical improvement. Cerebral MRI and EEG helped diagnosis, follow-up of the encephalitis, and evolution after treatment., Competing Interests: None declared., (Thieme. All rights reserved.)

Charcot-Marie-Tooth disease type 1A (CMT1A) is related to PMP22 gene duplication. It is characterized at electrodiagnostic testing (EDX) by diffuse homogeneous signs of demyelination, such as velocity slowing and prolonged distal latencies. These abnormalities are less pronounced in infants under two years old, and the possibility of normal nerve conduction studies (NCS) in infants with CMT1A under one year of age has been questioned. We report three infants who displayed normal or almost normal NCS. EDX abnormalities in CMT1A patients may therefore appear late during development. This may affect early EDX diagnosis in infants and should be considered for upcoming clinical trials., Competing Interests: Declaration of Competing Interest No funding. The authors have no conflicts of interest related with this article., (Copyright © 2022 Elsevier Masson SAS. All rights reserved.)

Background: The monitoring of head circumference (HC) is essential to early detect any conditions affecting its growth in early childhood. A positive secular trend and regional specificities in HC suggested the need to provide updated national HC reference growth charts., Methods: We extracted all growth data collected from 42 primary-care physicians from across the French metropolitan territory who used the same electronic medical-records software. We selected HC measurements up to age five years for all children who were born after 1990 with birth weight > 2500 g. We derived new HC growth charts by using Generalized Additive Models for Location, Scale and Shape, then externally validated them until 30 months of age by comparison with the national population-based Étude Longitudinale Française depuis l'Enfance (ELFE) birth cohort and compared them to previous French and WHO growth charts., Findings: With 973,869 HC measurements from 157,762 children, new calibrated HC growth charts from birth to age five years were generated. The new HC growth charts showed good external fit by comparison with the ELFE birth cohort. As compared with the new HC growth charts, the previous French and WHO growth charts mean HC z-scores were, respectively, -0.4 and -0.6 SD for girls and -0.2 and -0.6 SD for boys., Interpretation: We produced and validated national calibrated HC growth charts by using a novel big-data approach applied to data routinely collected in clinical practice. Comparison with previous French and WHO growth charts confirmed a positive secular trend since the 1960s and regional specificities., Funding: The French Ministry of Health; Laboratoires Guigoz-General Pediatrics section of the French Society of Pediatrics-Paediatric Epidemiological Research Group; the French Association of Ambulatory Pediatrics; and educational grant from the Regional Health Agency of Ile-de-France., Competing Interests: BH, AW, MC, BF and PS are co-owners of the patent for the new national French AFPA/Inserm/CGM growth charts. All remaining authors declare no competing interests., (© 2021 The Authors.)

The aim of this study was to evaluate the frequency of neurodevelopmental disorders (NDD) in children with significant congenital heart disease (CHD) and to determine associated factors to NDD and frequency of follow-up in developmental therapies. Two hundred and ten children with significant CHD aged from 6 to 66 months were enrolled over a period of six months. The Ages & Stages Questionnaire Third Edition in French (ASQ-3) was used to assess neurodevelopmental domains. NDD were defined if cut-off scores were ≤ - 1SD. - 1SD corresponded to "Monitor" range: children with minor or emerging disorders; - 2SD corresponded to "Refer" range: children exhibiting neurodevelopmental delays. Forty children were in "Monitor" range and 86 in "Refer" range. NDD rate was 60.0% (n = 126, 95% CI, 53.4 to 66.6%). There was no difference regarding CHD severity (p = 0.99). Only the presence of non-cardiac disease (OR = 2.14; 95% CI, 1.11 to 4.20) was associated with NDD. Forty-six children with NDD had no developmental follow-up (among them 21 were in "Refer" range (10%)) despite this being available.Conclusion: Children with significant CHD are at risk for NDD regardless of CHD severity. Systematic and early monitoring in a specific care program is required. Barriers that prevent access of care must be identified.Trial registration: Neurodevelopmental Disorders in Children With Congenital Heart Disease. NeuroDis-CHD. NCT03360370. https://clinicaltrials.gov/ct2/show/NCT03360370 What is Known: • Children with CHD are at risk for neurodevelopmental disorders and behavioural problems impacting their social adaptation, academic achievements and quality of personal and family life even in adulthood. What is New: • Children with CHD are at risk for neurodevelopmental disorders regardless of the complexity of the CHD. • Even with the availability of appropriate developmental services, children with CHD are not correctly followed, highlighting the need of a specific program of care for a better outcome. Local barriers that prevent access of care of those children must be identified.

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., (© The Author(s) (2019). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Catatonia is a rare, underdiagnosed syndrome in children. We report the case of a 4-year-old child admitted for recent social withdrawal alternating with psychomotor excitement, verbigeration, and a loss of toilet readiness. He had a history of neonatal seizures, had been stabilized with vigabatrin, and was seizure free without treatment for several months. The pediatric and psychiatric examination revealed motor stereotypes, mannerism, bilateral mydriasis, and visual hallucinations. Laboratory and brain imaging explorations were initially negative. Catatonic symptoms, as measured with the Pediatric Catatonia Rating Scale, significantly decreased after introducing lorazepam, the first-line recommended treatment of this condition. On the basis of the neonatal seizure history, complementary genetic investigations were performed and revealed a mutation in the SCN2A gene, which encodes the voltage-gated sodium channel Nav1.2. Catatonic symptoms progressively disappeared after reintroducing vigabatrin. At the syndromic level, catatonia in young children appears responsive to high-dose lorazepam and is well monitored by using the Pediatric Catatonia Rating Scale. This case reveals the need for wide-ranging explorations in early-onset catatonia because specific targeted treatments might be available., Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2018 by the American Academy of Pediatrics.)

Objective: This study was undertaken to assess the utility of the Ages and Stages Questionnaire-3rd Edition (ASQ-3) and the Vineland Adaptive Behavior Scales-2nd Edition (VABS-II) as neurodevelopmental screening tools for infants exposed to antiseizure medications in utero, and to examine their suitability for use in large-population signal generation initiatives., Methods: Participants were women with epilepsy who were recruited from 21 hospitals in England and Northern Ireland during pregnancy between 2014 and 2016. Offspring were assessed at 24 months old using the Bayley Scales of Infant Development-3rd Edition (BSID-III), the VABS-II, and the ASQ-3 (n = 223). The sensitivity and specificity of the ASQ-3 and VABS-II to identify developmental delay at 24 months were examined, using the BSID-III to define cases., Results: The ASQ-3 identified 65 children (29.1%) as at risk of developmental delay at 24 months using standard referral criteria. Using a categorical approach and standard referral criteria to identify delay in the ASQ-3 and BSID-III at 24 months, the ASQ-3 showed excellent sensitivity (90.9%) and moderate specificity (74.1%). Utilizing different cut-points resulted in improved properties and may be preferred in certain contexts. The VABS-II exhibited the strongest psychometric properties when borderline impairment (>1 SD below the mean) was compared to BSID-III referral data (sensitivity = 100.0%, specificity = 96.6%)., Significance: Both the ASQ-3 and VABS-II have good psychometric properties in a sample of children exposed to antiseizure medications when the purpose is the identification of at-risk groups. These findings identify the ASQ-3 as a measure that could be used effectively as part of a tiered surveillance system for teratogenic exposure by identifying a subset of individuals for more detailed investigations. Although the VABS-II has excellent psychometric properties, it is more labor-intensive for both the research team and participants and is available in fewer languages than the ASQ-3., (© 2024 The Authors. Epilepsia published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)

Background No study dedicated to postdrome symptoms of migraine attacks is available in children and adolescents. Objective To study the resolution phase of the migraine attack in children and adolescents. Methods 100 children and adolescents with ICHD-3 beta migraine without and/or with typical aura were included. Each patient, and one of her/his parents, were interviewed by phone about the postdrome phrase of their last six months' migraine attacks. They were specifically instructed to distinguish symptoms that had begun before and went on after migraine headache cessation (referred to as persistent symptoms), and symptoms whose onset was strictly after headache cessation (referred to as true postdromes). Results 91% of patients reported persistent symptoms, with a mean of 2.9 and a median of 2; asthenia, cognitive difficulties, pallor, cognitive slowing, anorexia, somnolence, and nausea were the most frequently reported. They lasted less than 12 h in 71% of patients. True postdromes were reported by 82% of patients, with a mean of 2.6 and a median of 2; thirst, somnolence, visual disturbances, food craving, paraesthesias, and ocular pain being the most frequently reported. They lasted less than 12 h in 94% of patients. Conclusions This study showed that children and adolescents with migraine had both frequent persistent symptoms and true postdromes. Both were notably different from those reported in adults.

Standardized terminology for computer-based assessment and reporting of EEG has been previously developed in Europe. The International Federation of Clinical Neurophysiology established a taskforce in 2013 to develop this further, and to reach international consensus. This work resulted in the second, revised version of SCORE (Standardized Computer-based Organized Reporting of EEG), which is presented in this paper. The revised terminology was implemented in a software package (SCORE EEG), which was tested in clinical practice on 12,160 EEG recordings. Standardized terms implemented in SCORE are used to report the features of clinical relevance, extracted while assessing the EEGs. Selection of the terms is context sensitive: initial choices determine the subsequently presented sets of additional choices. This process automatically generates a report and feeds these features into a database. In the end, the diagnostic significance is scored, using a standardized list of terms. SCORE has specific modules for scoring seizures (including seizure semiology and ictal EEG patterns), neonatal recordings (including features specific for this age group), and for Critical Care EEG Terminology. SCORE is a useful clinical tool, with potential impact on clinical care, quality assurance, data-sharing, research and education., (Copyright © 2017 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Aim: There is a need for methods that can provide valid assessment tools in a follow-up programme without great financial costs. This study assessed the accuracy of the 60-month Ages and Stages Questionnaire as a screening tool to predict a low intelligence quotient score at 6 years in children born very preterm., Methods: Totally, 54 children participated in a six-year follow-up study, which included an intelligence quotient test at 6 years of age and a 60-month Ages and Stages Questionnaire at four and a half or 5 years of age at respond. We used the receiver operating characteristic curve and evaluated the optimal cut-off score to predict a low intelligence quotient score., Results: At four and a half years, the optimal cut-off value for predicting a low intelligence quotient score was 242, with a sensitivity of 67% and a specificity of 59%. At 5 years, only one child had a low intelligence quotient score, and the analysis was not performed., Conclusion: Our results did not support the use of the 60-month Ages and Stages Questionnaire as a valuable screening tool to predict a low intelligence quotient score in children born very preterm at 6 years of age., (© 2023 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.)

Aim: The objective of this study was to investigate the involvement of the motor fibres of the corpus callosum after unilateral neonatal arterial ischemic stroke (NAIS) of the middle cerebral artery territory and the relationship to both ipsilesional and contralesional hand function., Method: Using high-resolution structural magnetic resonance imaging (MRI), functional MRI, and magnetic resonance diffusion-tractography, we compared the midsagittal area of the motor part of the corpus callosum (defined by the fibres connecting the precentral gyri) between 33 7-year-old children after unilateral NAIS and 31 typically developing 7-year-old children. Hand motor performance was assessed by the box and blocks test., Results: Children after NAIS showed on average significantly smaller motor corpus callosum area compared to typically developing children (p<0.001, without differences of the non-motor corpus callosum area). In addition, there was a significant positive association between the motor part of the corpus callosum and both contralesional (Pr(>|t|)=0.034) and ipsilesional hand motor performance (Pr(>|t|)=0.006) after controlling for lesion volume and sex. In a post-hoc analysis the additional contribution of corticospinal tract damage was evaluated., Interpretation: Compared to typically developing children, children after NAIS exhibited a smaller motor part of their corpus callosum associated with reduced contralesional but also ipsilesional manual dexterity. These results indicate that the affection of transcallosal motor fibres in unilateral NAIS might be of functional relevance and an important part of the involved structural network that should be elucidated in further studies., (© 2017 Mac Keith Press.)

Neonatal monitoring and other explorations required just after neonatal arterial ischemic stroke (NAIS) diagnosis remain elusive. This review attempts to propose guidelines on this topic. During neonatal period, three major contexts related to NAIS emerge: 1) Metabolic disorders including hypoglycemia; 2) Early post-natal infections; 3) Cardio-vascular anomalies. Different patient profiles have been defined (typical, atypical and at risk profiles). According to these profiles, a final decisional tree including biological monitoring and complementary explorations has been suggested to caregivers., (© 2017 Elsevier Masson SAS. Tous droits réservés.)