RESUMO
AIM: Infants born preterm are at risk of cerebral palsy (CP) and motor or cognitive developmental delay. For clinicians, it is essential to know the relative predictive accuracy of the most commonly used neuroimaging and neurophysiological tests for the early prediction of adverse neurodevelopmental outcome. The aim of this study was to compare the accuracy of these tests in survivors of a population of infants born very preterm. METHOD: A retrospective cohort study was performed in 163 children born before 32 weeks gestational age. We compared the accuracy in predicting adverse neurodevelopmental outcome at the age of 2 years 6 months of early and late cranial ultrasound (CUS), magnetic resonance imaging, somatosensory evoked potentials after stimulation of the posterior tibial nerve, and electroencephalography by calculating positive and negative likelihood ratios. RESULTS: An abnormal early CUS is the best predictor of the presence of CP (positive likelihood ratio 6.09), motor developmental delay (positive likelihood ratio 3.11), and cognitive developmental delay (positive likelihood ratio 5.66). Overall, negative likelihood ratios were poor, ranging between 0.49 and 0.98, meaning that a normal test result had only minimal influence on the probability of adverse neurological outcome. INTERPRETATION: None of the diagnostic tests had a good performance in predicting future neurodevelopmental problems in infants born preterm. A normal test result provided very little clinically useful information. WHAT THIS PAPER ADDS: An abnormal early cranial ultrasound (positive test result) is the best predictor of adverse neurodevelopmental outcome. All negative results have poor predictive value of future neurodevelopmental problems.
Assuntos
Encéfalo/diagnóstico por imagem , Deficiências do Desenvolvimento/diagnóstico por imagem , Deficiências do Desenvolvimento/fisiopatologia , Ecoencefalografia , Potenciais Somatossensoriais Evocados/fisiologia , Lactente Extremamente Prematuro , Paralisia Cerebral/diagnóstico , Paralisia Cerebral/etiologia , Distribuição de Qui-Quadrado , Pré-Escolar , Transtornos Cognitivos/diagnóstico , Transtornos Cognitivos/etiologia , Estudos de Coortes , Feminino , Idade Gestacional , Humanos , Imageamento por Ressonância Magnética , Masculino , Exame NeurológicoRESUMO
OBJECTIVE: KCNQ2 and KCNQ3 mutations are known to be responsible for benign familial neonatal seizures (BFNS). A few reports on patients with a KCNQ2 mutation with a more severe outcome exist, but a definite relationship has not been established. In this study we investigated whether KCNQ2/3 mutations are a frequent cause of epileptic encephalopathies with an early onset and whether a recognizable phenotype exists. METHODS: We analyzed 80 patients with unexplained neonatal or early-infantile seizures and associated psychomotor retardation for KCNQ2 and KCNQ3 mutations. Clinical and imaging data were reviewed in detail. RESULTS: We found 7 different heterozygous KCNQ2 mutations in 8 patients (8/80; 10%); 6 mutations arose de novo. One parent with a milder phenotype was mosaic for the mutation. No KCNQ3 mutations were found. The 8 patients had onset of intractable seizures in the first week of life with a prominent tonic component. Seizures generally resolved by age 3 years but the children had profound, or less frequently severe, intellectual disability with motor impairment. Electroencephalography (EEG) at onset showed a burst-suppression pattern or multifocal epileptiform activity. Early magnetic resonance imaging (MRI) of the brain showed characteristic hyperintensities in the basal ganglia and thalamus that later resolved. INTERPRETATION: KCNQ2 mutations are found in a substantial proportion of patients with a neonatal epileptic encephalopathy with a potentially recognizable electroclinical and radiological phenotype. This suggests that KCNQ2 screening should be included in the diagnostic workup of refractory neonatal seizures of unknown origin.
Assuntos
Epilepsia Neonatal Benigna/diagnóstico , Epilepsia Neonatal Benigna/genética , Canal de Potássio KCNQ2/genética , Mutação/genética , Fenótipo , Criança , Pré-Escolar , Epilepsia Neonatal Benigna/fisiopatologia , Feminino , Humanos , MasculinoRESUMO
Mutations in STXBP1 have been identified in a subset of patients with early onset epileptic encephalopathy (EE), but the full phenotypic spectrum remains to be delineated. Therefore, we screened a cohort of 160 patients with an unexplained EE, including patients with early myoclonic encephalopathy (EME), Ohtahara syndrome, West syndrome, nonsyndromic EE with onset in the first year, and Lennox-Gastaut syndrome (LGS). We found six de novo mutations in six patients presenting as Ohtahara syndrome (2/6, 33%), West syndrome (1/65, 2%), and nonsyndromic early onset EE (3/64, 5%). No mutations were found in LGS or EME. Only two of four mutation carriers with neonatal seizures had Ohtahara syndrome. Epileptic spasms were present in five of six patients. One patient with normal magnetic resonance imaging (MRI) but focal seizures underwent epilepsy surgery and seizure frequency dropped drastically. Neuropathology showed a focal cortical dysplasia type 1a. There is a need for additional neuropathologic studies to explore whether STXBP1 mutations can lead to structural brain abnormalities.
Assuntos
Predisposição Genética para Doença/genética , Proteínas Munc18/genética , Mutação/genética , Convulsões/genética , Convulsões/cirurgia , Espasmos Infantis/genética , Encéfalo/metabolismo , Encéfalo/patologia , Criança , Pré-Escolar , Eletroencefalografia , Feminino , Humanos , Lactente , Masculino , Fosfopiruvato Hidratase/metabolismo , Convulsões/etiologia , Convulsões/patologia , Espasmos Infantis/complicações , Adulto JovemRESUMO
Sleep is a key process in neurodevelopment and essential for the maturation of fundamental brain functions. Premature birth can disturb the initial steps of sleep maturation, which may contribute to the impairment of neurodevelopment. It is thus fundamental to understand the maturation of the various sleep states and the quality of cerebral function in each vigilance state, as well as the development of sleep cyclicity, in at-risk neonatal infants, particularly those born premature. The objective of this review is to provide a precise description of sleep states and cycles and their rhythmic organization in premature and term newborns according to their gestational age. Technical aspects of polysomnography, which requires a high level of expertise in neonates, are also described. Principles of the visual interpretation of polysomnography, including the simultaneous analysis of behavioral (spontaneous motricity and eye movements), polysomnographic parameters (electro-oculogram, electrocardiogram, respiration), and electroencephalography patterns are presented. The neurophysiology of sleep ontogenesis and its interaction with brain maturation are discussed, highlighting the crucial role of sleep states and their duration in premature newborns. In particular, the involvement of myoclonic twitches in functional connectivity in sensorimotor development is discussed. Indeed, sleep quality, determined by combined polysomnographic parameters, reflects either normal or pathological developmental processes during the neonatal period. The fundamental place of neurophysiological explorations in the early detection of sleep disorders is discussed, as well as their potential consequences on neurodevelopmental care to improve the prevention of neurodevelopmental impairment.
Assuntos
Sono , Ontologias Biológicas , Eletroencefalografia , Eletroculografia , Feminino , Humanos , Recém-Nascido , Polissonografia , Gravidez , VigíliaRESUMO
Electroencephalography (EEG) of neonatal patients is amongst the most valuable diagnostic and prognostic tool. EEG recordings, acquired at the bedside of infants, evaluate brain function and the maturation of premature and extremely premature infants. Strict conditions of acquisition and interpretation must be respected to guarantee the quality of the EEG and ensure its safety for fragile children. This article provides guidance for EEG acquisition including: (1) the required equipment and devices, (2) the modalities of installation and asepsis precautions, and (3) the digital signal acquisition parameters to use during the recording. The fundamental role of a well-trained technician in supervising the EEG recording is emphasized. In parallel to the acquisition recommendations, we present a guideline for EEG interpretation and reporting. The successive steps of EEG interpretation, from reading the EEG to writing the report, are described. The complexity of the EEG signal in neonates makes artefact detection difficult. Thus, we provide an overview of certain characteristic artefacts and detail the methods for eliminating them.
Assuntos
Eletroencefalografia , Artefatos , Humanos , Recém-Nascido , Recém-Nascido PrematuroRESUMO
Electroencephalography (EEG) is the reference tool for the analysis of brain function, reflecting normal and pathological neuronal network activity. During the neonatal period, EEG patterns evolve weekly, according to gestational age. The first analytical criteria for the various maturational stages and standardized neonatal EEG terminology were published by a group of French neurophysiologists training in Paris (France) in 1999. These criteria, defined from analog EEG, were completed in 2010 with digital EEG analysis. Since then, this work has continued, aided by the technical progress in EEG acquisition, the improvement of knowledge on the maturating processes of neuronal networks, and the evolution of critical care. In this review, we present an exhaustive and didactic overview of EEG characteristics from extremely premature to full-term infants. This update is based on the scientific literature, enhanced by the study of normal EEGs of extremely premature infants by our group of neurophysiologists. For educational purposes, particular attention has been paid to illustrations using new digital tools.
Assuntos
Eletroencefalografia , Recém-Nascido Prematuro , Encéfalo , França , Idade Gestacional , Humanos , Recém-NascidoRESUMO
Steroids and adrenocorticotrophic hormone (ACTH) have been used for the treatment of infantile spasms for several years. However, the use of steroids in the treatment of epilepsy beyond infantile spasms has been limited to only a few studies. We report the experience with steroids in 32 children with intractable epilepsy, not including West syndrome. In 47% there was a decrease in seizure frequency, 25% became seizure free, 11% had a seizure reduction of >50% and 11% had a seizure reduction of <50%. Our study confirms the conclusions of few previous reports of effective adjunctive steroid treatment for children with intractable epilepsy. The possible side effects, however, especially during prolonged therapy remain an important concern.
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Anticonvulsivantes/uso terapêutico , Epilepsia/tratamento farmacológico , Esteroides/uso terapêutico , Administração Oral , Hormônio Adrenocorticotrópico/administração & dosagem , Hormônio Adrenocorticotrópico/uso terapêutico , Anticonvulsivantes/administração & dosagem , Anticonvulsivantes/efeitos adversos , Criança , Pré-Escolar , Resistência a Medicamentos , Feminino , Humanos , Injeções Intramusculares , Masculino , Recidiva , Estudos Retrospectivos , Esteroides/administração & dosagem , Esteroides/efeitos adversosRESUMO
UNLABELLED: Huntington disease (HD) is an autosomal dominant, lethal neurodegenerative disorder of the central nervous system, caused by an uncontrolled expansion of a CAG dynamic mutation in the coding region of the IT15gene. Although a majority of patients have a midlife onset of the disease, in a small number of patients the disease manifests before 20 years of age. In adults, HD is mainly characterised by involuntary movements, personality changes and dementia. By contrast, in children a dominant picture of bradykinesia, rigidity, dystonia and epileptic seizures is noticed. The earlier onset is often associated with a paternal transmission of the disease allele to the offspring. We report here a rather unusual infantile onset of the disease in a little girl who presented with a history of seizures and psychomotor regression starting at the age of 3 years. A progressive cortical-subcortical atrophy, progressive cerebellar atrophy and lesions in the basal ganglia were found on MRI. An important expansion, of 214 triplet numbers, of the CAG repeat size associated with HD, was observed. CONCLUSION: Juvenile Huntingdon disease should be considered in children suffering from a progressive neurodegenerative disease.