Evaluación funcional de niños, niñas y adolescentes con diagnóstico de trastorno del espectro autista en Argentina: estudio multicéntrico TEA-CIFunciona / Functional assessment of children and adolescents with autism spectrum disorder in Argentina: ICF-ASD multicenter study

Introducción. El trastorno del espectro autista (TEA) se caracteriza por dificultades de comunicación social y comportamientos repetitivos y estereotipados. Además de la categoría diagnóstica, las actividades que los niños, niñas y adolescentes (NNyA) pueden realizar y la participación social son los aspectos principales por considerar desde el marco de la Clasificación Internacional del Funcionamiento, la Discapacidad y la Salud (CIF), propuesta por la Organización Mundial de la Salud, para describir los estados de salud. En una investigación previa, elaboramos la primera versión de una herramienta pediátrica basada en la CIF llamada TEA-CIFunciona para evaluación funcional de NNyA con diagnóstico de TEA, que permitió captar características funcionales adaptadas a nuestro contexto cultural. Se propuso como objetivo posterior aplicar TEA-CIFunciona en formato multicéntrico para evaluar NNyA de diferentes regiones, revisar y actualizar la herramienta, e identificar barreras y facilitadores. Población y métodos. Se administró TEA-CIFunciona versión 1.0 a NNyA con diagnóstico confirmado de TEA (según criterios del DSM-5), menores de 16 años, en seguimiento en cinco centros de atención pediátrica del país. Resultados. Se obtuvo la versión 2.0 de TEA-CIFunciona con 34 categorías (10 funciones corporales, 15 actividades y participación, y 9 factores ambientales). Se elaboró el perfil funcional de la muestra completa (n = 308). Conclusiones. La versión actualizada de TEA-CIFunciona contribuye a estandarizar y a sistematizar la obtención de información necesaria para adecuar el seguimiento de los NNyA con TEA a nivel nacional. Además, permite identificar barreras por superar y facilitadores para generalizar

Introduction. Autism spectrum disorder (ASD) is characterized by difficulties in social communication and repetitive and stereotyped behaviors. In addition to the diagnostic category, the activities performed by children and adolescents and their social involvement are the main aspects to be considered according to the International Classification of Functioning, Disability, and Health (ICF) proposed by the World Health Organization to describe health status. In a previous study, we developed the first version of a pediatric tool based on the ICF called ICF-ASD for the functional assessment of children and adolescents with ASD to capture functional characteristics adapted to our cultural setting. Our subsequent objective was to apply the ICF-ASD in a multicenter format to assess children and adolescents from different regions, review, and update it, and identify barriers and facilitators. Population and methods. The ICF-ASD version 1.0 was administered to children and adolescents younger than 16 years with a confirmed diagnosis of ASD (as per DSM-5 criteria), who were receiving follow-up at 5 children's health centers across Argentina. Results. Version 2.0 of the ICF-ASD was obtained, which included 34 categories (10 under body function, 15 under activities and participation, and 9 under environmental factors). A functional profile was developed for the whole sample (n = 308). Conclusions. The updated version of the ICF-ASD helps to standardize and systematize the collection of necessary data for an adequate follow-up of children and adolescents with ASD at a national level. It also allows to identify barriers to overcome and facilitators to be generalized

[Decreased vision due to hypovitaminosis A in children with food selectivity]. / Disminución visual por hipovitaminosis A en niños con selectividad alimentaria.

INTRODUCTION: Vitamin A deficiency can cause eye disease and has been related to food selectivity in children with autism spectrum disorder (ASD). METHODS: A series of 13 pediatric patients with severe ophthalmological involvement as an initial manifestation of hypovitaminosis A is described. RESULTS: With significant Vitamin A deficiency, neuroimaging was performed in 11 patients. Of these, 8 had pathological findings with the presence of cranial hyperostosis. Lumbar puncture was performed in these patients and endocranial hypertension was detected in 7 of the 8 patients. All had food selectivity and 61.5% had ASD. CONCLUSIONS: Toxic-nutritional optic neuropathy is a rare pathology in children and presents with progressive, bilateral and painless visual loss due to damage to the optic nerve, which can generate severe and irreversible damage to it. Food history allows early detection of nutrient deficiencies in children with restrictive feeding, especially in neuro-atypical patients. This is essential to implement preventive measures and treatment with vitamin A in order to avoid irreversible consequences.

Introducción: La deficiencia de vitamina A puede producir enfermedad ocular y se ha relacionado con la selectividad alimentaria en niños con trastorno del espectro autista (TEA). Métodos: Se describen una serie de 13 pacientes pediátricos con compromiso oftalmológico grave como manifestación inicial de hipovitaminosis A. Resultados: Con deficiencia significativa de Vitamina A, en 11 pacientes se realizaron neuroimágenes. De ellos, 8 tuvieron resultados patológicos con presencia de hiperostosis craneal. En estos se realizó punción lumbar y en 7 de los 8 pacientes se detectó hipertensión endocraneana. Todos tenían selectividad alimentaria y el 61.5 % TEA. Conclusiones: La neuropatía óptica toxico-nutricional es una enfermedad poco frecuente en niños y se presenta con pérdida visual progresiva, bilateral e indolora debido al daño del nervio óptico, pudiendo generar lesión severa e irreversible del mismo. La anamnesis alimentaria permite la pesquisa temprana de deficiencias de nutrientes en niños con alimentación restrictiva, especialmente en pacientes neuro atípicos. Esto es esencial para implementar medidas de prevención y el tratamiento con vitamina A con el fin de evitar consecuencias irreversibles.

Level of support/commitment and behavior during mealtime and dental care negatively impact the dental caries prevalence in autistic individuals: cross-sectional study.

OBJECTIVE: To verify whether factors associated with Autism Spectrum Disorder (ASD) would have impact on the dental-caries prevalence. MATERIALS AND METHODS: All ASD-individuals receiving care in a specialized center with minimum of 4y old were recruited. Demographic, socioeconomic and behavioral characteristics, level of support/commitment (Childhood Autism Rating Scale), mealtime behavior (Brief Autism Mealtime Behavior Inventory) and medication use were answered by ASD-individual's parents. Behavior during dental care was evaluated from Frankl scale. Dental-caries prevalence was the primary outcome. Three examiners calibrated/trained collected the data. Chi-square test was used to compare the variables impact on the dental-caries prevalence. RESULTS: 61 ASD-individuals were potentially eligible, and the all parents/guardians consent to participate. Dental-caries prevalence was 42.9%, which was statistically associated with lower toothbrushing frequency, higher level of support/commitment, and worse behavior at meals and during in dental care. Dental-caries prevalence was approximately higher twice in ASD-individuals: (i) uncooperative with dental care when compared those cooperative (62% versus 32%, respectively); (ii) with severe level of support when compared to those with mild/moderate level (58% versus 28%, respectively); and (iii) with worse mealtime behavior when compared to those with better behavior (59% versus 28%, respectively). A medium statistical correlation was observed between support level and mealtime behavior (rS=0.39). The BAMBI component statistically associated with dental-caries prevalence was the food refusal (capture problem when a child rejects a presented food, crying, spitting out food). CONCLUSION: higher required level of support, worse mealtime behavior and uncooperative profile in dental care negatively affect the dental-caries prevalence. CLINICAL RELEVANCE: our findings provide evidence of the need of specialized, preventive and individualized dental care among ASD-individuals.

Síndrome do QT longo em criança assintomática com mutação LMNA e TTN. Uma doença em constante evolução / Long QT syndrome in an asymptomatic child with LMNA e TTN mutation. A constantly evolving disease

INTRODUÇÃO: Quadros de síndrome de QT longo (SQTL) são responsáveis pela maioria dos casos de morte súbita (MS) em coração estruturalmente normal. Desde sua descrição inicial na forma autossômica dominante, o diagnóstico e novas variantes encontram-se em evolução. O avanço da medicina de precisão e o maior uso do Exoma, evidencia cada vez mais quadros de overlap entre doenças elétricas e miocárdicas genéticas. Mutações no LMNA associam-se à miocardiopatia dilatada, MS por arritmia ventricular, bradicardia e bloqueio atrioventricular avançado. Mutações no TTN também se associam à miocardiopatia dilatada. Até o momento, esses genes não estão associados à SQTL. OBJETIVO: Relatar caso em criança com fenótipo de SQTL, escore de Schwartz de alta probabilidade e mutações provavelmente patológicas nos genes LMNA e TTN na ausência de miocardiopatia dilatada. RELATO DO CASO: Masculino, 7 anos, sem história de MS familiar, com transtorno do espectro autista - TEA, sem queixas cardiológicas. Em avaliação pré-uso de medicação para TEA observou prolongamento do QTc e bradicardia (Tabela de Davignon). Apresentava QTc 563 ms e FC variável (70 a 100) em diversas avaliações eletrocardiográficas. O escore de Schwartz atribuído foi de 3,5. A avaliação ecocardiográfica e eletromiográfica não evidenciou doença cardíaca ou muscular. A avaliação genética por Exoma evidenciou variante provavelmente patogênica no LMNA(associada à miocardiopatia dilatada e distrofia muscular) e TTN (associada à cardiomiopatia hipertrófica e distrofia muscular). Receitado propranolol 3 mg kg dia, espironolactona 1 mg kg dia e reposição de magnésio 50 mg kg dia. Afamília foi orientada sobre sinais de alarme, medicações que prolongam o QTc e receberá treinamento de suporte básico de vida. Aavaliação genética familiar está em andamento. CONCLUSÃO: 1) ASQTL apresenta amplo espectro clínico e genético e seus estudos seguem em constante evolução 2) Novas variantes genéticas são possíveis e quadros de overlap se tornarão cada vez mais frequentes com a evolução e popularização da medicina de precisão 3) A abordagem do paciente deve ser multidisciplinar e incluir orientação genética, farmacológica, psicológica e treinamento em RCPpara adultos próximos à criança.

[Autism: associated medical conditions]. / Autismo: condiciones médicas asociadas.

Autism will accompany people throughout life with variations in its evolution and is frequently associated with other neurodevelopmental disorders (intellectual disability, attention deficit hyperactivity disorder, motor clumsiness, language disorder), neuropsychiatric disorders (depression, anxiety, schizophrenia, catatonia), epilepsy, sleep disorders, gastrointestinal disorders. In addition to the disorders typical of autism, we must consider an entire range of conditions, since their identification and adequate treatment will allow a better quality-of-life for people with autism. In 35% of cases, we can identify neurogenetic conditions which will allow us to prevent or identify associated medical entities. In this work we will analyze two groups, in a purely organizational way, medical conditions associated with defined entities (Down, Angelman, Fragile X, Rett, Phelan-McDermid and Timothy syndromes) and those that can be consistently associated in people with autism without an identified entity.

El autismo acompañará a las personas a lo largo de toda la vida, con variaciones en su evolución, está frecuentemente asociado a otros trastornos del neurodesarrollo (discapacidad intelectual, trastorno de déficit de atención e hiperactividad, torpeza motriz, trastorno del lenguaje), trastornos neuropsiquiátricos (depresión, ansiedad, esquizofrenia, catatonía), epilepsia, trastornos de sueño, trastornos gastrointestinales. Además de los trastornos propios del autismo, debemos tener en cuenta todo este abanico de condiciones, ya que su identificación y tratamiento permitirán una mejor calidad de vida. En el 35% de los casos podemos identificar entidades neurogenéticas, lo cual permitirá prevenir o identificar más rápidamente condiciones médicas asociadas. En este trabajo analizaremos dos grupos, de forma puramente organizativa, las condiciones médicas asociadas a entidades definidas (síndromes de Down, Angelman, X frágil, Rett, Phelan-McDermid y Timothy) y las que pueden asociarse consistentemente en personas con autismo sin una entidad identificada.

Effectiveness of Distance Educational Programs for parents of children diagnosed with Autism Spectrum Disorder: an integrative review. / Eficácia de Programas Educativos à Distância para pais de crianças com diagnóstico de Transtorno do Espectro Autista: uma revisão integrativa.

OBJECTIVE: to analyze the scientific literature on distance education programs for parents/caregivers in the development of children with Autism Spectrum Disorder (ASD). RESEARCH METHOD: the PICO strategy was used to identify the research problem. The databases Medline, ERIC, LILACs, EMBASE, CINAHL, Web of Science, and Scopus were searched using specific descriptors and free terms. There were no restrictions on time or language. Articles on online educational programs for parents of children with ASD were selected, focusing on the impact of these programs on the development of children up to six years old. SELECTION CRITERIA: studies were selected based on standard eligibility criteria, including full-text reading after initial screening using the RAYYAN software. Primary studies such as clinical trials and systematic reviews evaluating distance education programs for parents of children with ASD were included. DATA ANALYSIS: the RAYYAN software was used for initial study selection. Articles were hierarchically organized based on title and abstract, followed by full-text reading to apply eligibility criteria. RESULTS: the initial search yielded 1019 articles, of which 192 were identified as duplicates. After initial screening and full-text reading, 37 articles were analyzed, of which six were deemed eligible to answer the research question. Among the eligible studies, one was a systematic review and five were experimental studies. Experimental studies highlighted positive impacts on areas such as daily routines, behavioral flexibility, and communication. The systematic review provided preliminary evidence that distance education programs for parents can enhance knowledge about ASD, increase adherence to interventions, and foster the development of social and communication skills in children. CONCLUSION: the findings suggest that remote parent guidance programs may effectively improve knowledge about ASD, increase parent adherence to interventions, and promote the development of social and communication skills in children with ASD.

OBJETIVO: analisar a produção científica sobre programas educativos à distância para pais/responsáveis no desenvolvimento de crianças com Transtorno do Espectro Autista (TEA). ESTRATÉGIA DE PESQUISA: utilizou-se a estratégia PICO para identificar o problema de pesquisa. Foram consultadas as bases de dados Medline, ERIC, LILACs, EMBASE, CINAHL, Web of Science e Scopus utilizando descritores e termos livres específicos. não houve restrição de tempo ou idioma. Foram selecionados artigos sobre programas educativos online destinados a pais de crianças com TEA, com foco no impacto desses programas no desenvolvimento de crianças de até seis anos. CRITÉRIOS DE SELEçÃO: os estudos foram selecionados com base em critérios de elegibilidade padrões, incluindo a leitura completa dos artigos após a triagem inicial realizada com o software RAYYAN. Foram incluídos estudos primários, como ensaios clínicos e revisões sistemáticas que avaliaram programas educativos à distância para pais de crianças com TEA. ANÁLISE DOS DADOS: utilizou-se o software RAYYAN para a seleção inicial dos estudos. Os artigos foram organizados hierarquicamente com base no título e resumo, seguido pela leitura integral para aplicação dos critérios de elegibilidade. RESULTADOS: a busca inicial resultou em 1019 artigos, dos quais 192 foram identificados como duplicados. Após a seleção inicial e a leitura completa, 37 artigos foram analisados, dos quais seis foram considerados elegíveis para responder à pergunta de pesquisa. Entre os estudos elegíveis, um era uma revisão sistemática e cinco eram estudos experimentais. Os estudos experimentais destacaram impactos positivos em áreas como rotinas diárias, flexibilidade comportamental e comunicação. A revisão sistemática indicou evidências preliminares de que os programas educativos à distância para pais podem melhorar o conhecimento sobre TEA, aumentar a adesão às intervenções e promover o desenvolvimento de habilidades sociais e de comunicação nas crianças. CONCLUSÃO: os resultados sugerem que programas remotos de orientação para pais podem ser eficazes para melhorar o conhecimento sobre TEA, aumentar a adesão dos pais às intervenções e promover o desenvolvimento de habilidades sociais e de comunicação em crianças com TEA.

Stress in parents of preschoolers with Autism Spectrum Disorders: an update review.

BACKGROUND: Parental stress experienced in the context of caring for children with autism spectrum disorder (ASD) in preschool is significant and has been poorly studied; studies tend to focus on more advanced ages of children where parental symptomatology has become chronic. The current study sought to provide new empirical evidence on factors associated with parental stress. METHODS: An exhaustive search was conducted in four academic databases: CINAHL Complete, Medline Complete, Web of Science (WoS), and Scopus, limiting the articles to those published between 2017 and 2023. RESULTS: The sample obtained consisted of 24 selected articles, which were produced in 11 countries, and all were in English. In terms of content, the topics addressed were the manifestation of parental stress, factors of the child with ASD and their relationship with parental stress, factors of parents of children with ASD, family factors of parents of children with ASD, social factors of parents of children with ASD, parental stress and access to formal care services, and parental stress and specialized interventions. CONCLUSIONS: It is possible to affirm that research reports indicate that the general level of stress among parents of children with ASD is compared to their reference groups, both in relation to child-related stress and other stressors. The variables that affect parental stress exhibit a reciprocal influence among them, so interventions aimed at early childhood should incorporate both the children and their parental figures. This is in consideration of the impact that stress has on the mental health of parents, establishing that parents with better health have early access to support services during the early years of parenting, as well as in later years.

INTRODUCCIÓN: El estrés parental vivenciado en el contexto de cuidado de los niños con trastorno del espectro autistas en etapa preescolar es significativo y ha sido muy poco estudiado, las investigaciones tienden a focalizarse en edades de los niños más avanzada donde la sintomatología de los padres se ha cronificado. El objetivo de la presente investigación fue actualizar el corpus de evidencia empírica referida a los factores relacionados con el Estrés parental. MÉTODOS: Se realizó una búsqueda exhaustiva en cuatro bases de datos académicas: CINAHL Complete, Medline Complete, Web of Science (WoS) y Scopus, limitando los artículos publicados entre los años 2017 y 2023. RESULTADOS: La muestra obtenida fue de 24 artículos seleccionados, los cuales fueron producidos por 11 países todos de habla inglesa. En cuanto al contenido, los temas abordados son: La manifestación del estrés parental, factores del niño con TEA y su relación con el estrés parental, factores de los padres de los niños con TEA, factores familiares de los padres de los niños con TEA, factores sociales de los padres de los niños con TEA, estrés parental y acceso a los servicios formales de atención, y estrés parental e intervenciones especializadas. CONCLUSIONES: Es posible afirmar que las investigaciones reportan que el nivel general de estrés de los padres de niños con TEA es superior al de sus grupos de referencia, tanto en relación al estrés relacionado con el niño, como el que no. Las variables que afectan el estrés parental presentan una influencia recíproca entre éstas, por lo que las intervenciones dirigidas a la primera infancia deberían incorporar a los niños y a sus figuras parentales. Esto, en atención al impacto que el estrés presenta en la salud mental de los padres, estableciendo que los padres con mejor salud mental presentan mayor acceso temprano a los servicios de apoyo durante los primeros años de crianza, y en los años posteriores.

Impact of KDM6B mosaic brain knockout on synaptic function and behavior.

Autism spectrum disorders (ASD) are complex neurodevelopmental conditions characterized by impairments in social communication, repetitive behaviors, and restricted interests. Epigenetic modifications serve as critical regulators of gene expression playing a crucial role in controlling brain function and behavior. Lysine (K)-specific demethylase 6B (KDM6B), a stress-inducible H3K27me3 demethylase, has emerged as one of the highest ASD risk genes, but the precise effects of KDM6B mutations on neuronal activity and behavioral function remain elusive. Here we show the impact of KDM6B mosaic brain knockout on the manifestation of different autistic-like phenotypes including repetitive behaviors, social interaction, and significant cognitive deficits. Moreover, KDM6B mosaic knockout display abnormalities in hippocampal excitatory synaptic transmission decreasing NMDA receptor mediated synaptic transmission and plasticity. Understanding the intricate interplay between epigenetic modifications and neuronal function may provide novel insights into the pathophysiology of ASD and potentially inform the development of targeted therapeutic interventions.

Environmental pollutants as risk factors for autism spectrum disorders: a systematic review and meta-analysis of cohort studies.

BACKGROUND: Autism Spectrum Disorder (ASD) is a lifelong neurodevelopmental condition affecting communication, social interaction, and behavior. Evidence suggests that environmental pollutants are associated with ASD incidence. This review aimed to analyze the effect of environmental pollutants on ASD. METHODS: Systematic review and meta-analysis of cohort studies evaluated the association between exposure to environmental pollutants and ASD. We searched COCHRANE CENTRAL, MEDLINE, CINAHL, LILACS, EMBASE, PsycINFO, Web of Science, SciELO, and gray literature from inception to January 2023. The model used for meta-analysis was inverse variance heterogeneity (IVhet). The effect measures were the beta coefficient (ß) and the relative risk (RR) with their 95% confidence intervals (95% CI). Sensitivity analyses were carried out using an instrument to screen or diagnose autism. RESULTS: A total of 5,780 studies were identified; 27 were included in the systematic review, and 22 were included in the meta-analysis. These studies included 1,289,183 participants and 129 environmental pollutants. Individual meta-analyses found a significant association between nitrogen dioxide RR = 1.20 (95% CI: 1.03 to 1.38; I2: 91%), copper RR = 1.08 (95% CI: 1.03 to 1.13; I2: 0%), mono-3-carboxy propyl phthalate ß = 0.45 (95% CI: 0.20 to 0.70; I2: 0%), monobutyl phthalate ß = 0.43 (95% CI: 0.13 to 0.73; I2: 0%) and polychlorinated biphenyl (PCB) 138 RR = 1.84 (95% CI: 1.14 to 2.96; I2:0%) with ASD. Subgroup meta-analyses found a significant association with carbon monoxide RR = 1.57 (95% CI: 1.25 to 1.97; I2: 0%), nitrogen oxides RR = 1.09 (95% CI: 1.04 to 1.15; I2: 34%) and metals RR = 1.13 (95% CI: 1.01 to 1.27; I2:24%). CONCLUSION: This study found positive associations nitrogen dioxide, copper, mono-3-carboxypropyl phthalate, monobutyl phthalate, and PCB 138, and the development of ASD, likewise, with subgroups of pollutants carbon monoxide, nitrogen oxides, and metals. Therefore, it is important to identify these risk factors in children and adolescents to contribute to ASD and identify prevention strategies effectively.

An alpha 5-GABAA receptor positive allosteric modulator attenuates social and cognitive deficits without changing dopamine system hyperactivity in rats exposed to valproic acid in utero.

Autism spectrum disorders (ASDs) are characterized by core behavioral symptoms in the domains of sociability, language/communication, and repetitive or stereotyped behaviors. Deficits in the prefrontal and hippocampal excitatory/inhibitory balance due to a functional loss of GABAergic interneurons are proposed to underlie these symptoms. Increasing the postsynaptic effects of GABA with compounds that selectively modulate GABAergic receptors could be a potential target for treating ASD symptoms. In addition, deficits in GABAergic interneurons have been linked to dopamine (DA) system dysregulation, and, despite conflicting evidence, abnormalities in the DA system activity may underly some ASD symptoms. Here, we investigated whether the positive allosteric modulator of α5-containing GABAA receptors (α5-GABAARs) SH-053-2'F-R-CH3 (10 mg/kg) attenuates behavioral abnormalities in rats exposed to valproic acid (VPA) in utero, an established risk factor for autism. We also evaluated if animals exposed to VPA in utero present changes in the ventral tegmental area (VTA) DA system activity using in vivo electrophysiology and if SH-053-2'F-R-CH3 could attenuate these changes. SH-053-2'F-R-CH3 was administered intraperitoneally 30 min before each behavioral test and electrophysiology. In utero VPA exposure caused male and female rats to present increased repetitive behavior (self-grooming) in early adolescence and deficits in social interaction in adulthood. Male, but not female VPA rats, also presented deficits in recognition memory as adults. SH-053-2'F-R-CH3 attenuated the impairments in sociability and cognitive function in male VPA-exposed rats without attenuating the decreased social interaction in females. Adult male and female VPA-exposed rats also showed an increased VTA DA neuron population activity, which was not changed by SH-053-2'F-R-CH3. Despite sex differences, our findings indicate that α5-GABAARs positive allosteric modulators may effectively attenuate some core ASD symptoms.

Spontaneous Calcium Transients Recorded from Striatal Astrocytes in a Preclinical Model of Autism.

Autism spectrum disorder (ASD) is known as a group of neurodevelopmental conditions including stereotyped and repetitive behaviors, besides social and sensorimotor deficits. Anatomical and functional evidence indicates atypical maturation of the striatum. Astrocytes regulate the maturation and plasticity of synaptic circuits, and impaired calcium signaling is associated with repetitive behaviors and atypical social interaction. Spontaneous calcium transients (SCT) recorded in the striatal astrocytes of the rat were investigated in the preclinical model of ASD by prenatal exposure to valproic acid (VPA). Our results showed sensorimotor delay, augmented glial fibrillary acidic protein -a typical intermediate filament protein expressed by astrocytes- and diminished expression of GABAA-ρ3 through development, and increased frequency of SCT with a reduced latency that resulted in a diminished amplitude in the VPA model. The convulsant picrotoxin, a GABAA (γ-aminobutyric acid type A) receptor antagonist, reduced the frequency of SCT in both experimental groups but rescued this parameter to control levels in the preclinical ASD model. The amplitude and latency of SCT were decreased by picrotoxin in both experimental groups. Nipecotic acid, a GABA uptake inhibitor, reduced the mean amplitude only for the control group. Nevertheless, nipecotic acid increased the frequency but diminished the latency in both experimental groups. Thus, we conclude that striatal astrocytes exhibit SCT modulated by GABAA-mediated signaling, and prenatal exposure to VPA disturbs this tuning.

Zika virus vertical transmission induces neuroinflammation and synapse impairment in brain cells derived from children born with Congenital Zika Syndrome.

Zika virus (ZIKV) infection was first reported in 2015 in Brazil as causing microcephaly and other developmental abnormalities in newborns, leading to the identification of Congenital Zika Syndrome (CZS). Viral infections have been considered an environmental risk factor for neurodevelopmental disorders outcome, such as Autism Spectrum Disorder (ASD). Moreover, not only the infection per se, but maternal immune system activation during pregnancy, has been linked to fetal neurodevelopmental disorders. To understand the impact of ZIKV vertical infection on brain development, we derived induced pluripotent stem cells (iPSC) from Brazilian children born with CZS, some of the patients also being diagnosed with ASD. Comparing iPSC-derived neurons from CZS with a control group, we found lower levels of pre- and postsynaptic proteins and reduced functional synapses by puncta co-localization. Furthermore, neurons and astrocytes derived from the CZS group showed decreased glutamate levels. Additionally, the CZS group exhibited elevated levels of cytokine production, one of which being IL-6, already associated with the ASD phenotype. These preliminary findings suggest that ZIKV vertical infection may cause long-lasting disruptions in brain development during fetal stages, even in the absence of the virus after birth. These disruptions could contribute to neurodevelopmental disorders manifestations such as ASD. Our study contributes with novel knowledge of the CZS outcomes and paves the way for clinical validation and the development of potential interventions to mitigate the impact of ZIKV vertical infection on neurodevelopment.

Mental health in mothers of children with autism spectrum disorder: a cross-sectional study.

The increased prevalence of autism spectrum disorder (ASD) has placed a significant emotional and psychological burden on mothers. We explored the association between the severity of ASD symptoms in children and the mental health of their mothers during the COVID-19 pandemic. Our study included 1,924 mothers of children with ASD, enrolled in a web-based cross-sectional survey over 85 consecutive days to gather clinical and sociodemographic data. The severity of ASD symptoms was obtained according to the children's age. Using the Depression, Anxiety, and Stress Scales (DASS-21) scale, we found that 35.8 percent of mothers experienced both anxiety and depression. A high education level and a high family income reduced the chance of concurrent anxiety and depression. Conversely, unemployment, a child using psychiatric medication, and higher severity of ASD symptoms increased the chance. Notably, the severity of the ASD symptom was the sole predictor of maternal co-occurring anxiety and depression across all age groups (<3 years aOR = 2.04, 95%CI 1.07-3.89; 3-5 years aOR = 2.76, 95%CI 1.67-4.56; ≥ 6 years aOR = 1.61, 95%CI 1.04-2.50). Recognizing the challenges associated with ASD leads to greater acceptance and tailored interventions, ultimately improving the overall well-being of both individuals with ASD and their mothers.

The Interplay of Astrocytes and Neurons in Autism Spectrum Disorder.

Autism spectrum disorder (ASD) comprises a complex neurodevelopmental condition characterized by an impairment in social interaction, involving communication deficits and specific patterns of behaviors, like repetitive behaviors. ASD is clinically diagnosed and usually takes time, typically occurring not before four years of age. Genetic mutations affecting synaptic transmission, such as neuroligin and neurexin, are associated with ASD and contribute to behavioral and cognitive deficits. Recent research highlights the role of astrocytes, the brain's most abundant glial cells, in ASD pathology. Aberrant Ca2+ signaling in astrocytes is linked to behavioral deficits and neuroinflammation. Notably, the cytokine IL-6 overexpression by astrocytes impacts synaptogenesis. Altered neurotransmitter levels, disruptions in the blood-brain barrier, and cytokine dysregulation further contribute to ASD complexity. Understanding these astrocyte-related mechanisms holds promise for identifying ASD subtypes and developing targeted therapies.

Overnight Electroencephalogram to Forecast Epilepsy Development in Children with Autism Spectrum Disorders.

OBJECTIVE: To establish the utility of long-term electroencephalogram (EEG) in forecasting epilepsy onset in children with autism spectrum disorder (ASD). STUDY DESIGN: A single-institution, retrospective analysis of children with ASD, examining long-term overnight EEG recordings collected over a period of 15 years, was conducted. Clinical EEG findings, patient demographics, medical histories, and additional Autism Diagnostic Observation Schedule data were examined. Predictors for the timing of epilepsy onset were evaluated using survival analysis and Cox regression. RESULTS: Among 151 patients, 17.2% (n = 26) developed unprovoked seizures (Sz group), while 82.8% (n = 125) did not (non-Sz group). The Sz group displayed a higher percentage of interictal epileptiform discharges (IEDs) in their initial EEGs compared with the non-Sz group (46.2% vs 20.0%, P = .01). The Sz group also exhibited a greater frequency of slowing (42.3% vs 13.6%, P < .01). The presence of IEDs or slowing predicted an earlier seizure onset, based on survival analysis. Multivariate Cox proportional hazards regression revealed that the presence of any IEDs (HR 3.83, 95% CI 1.38-10.65, P = .01) or any slowing (HR 2.78, 95% CI 1.02-7.58, P = .046 significantly increased the risk of developing unprovoked seizures. CONCLUSION: Long-term EEGs are valuable for predicting future epilepsy in children with ASD. These findings can guide clinicians in early education and potential interventions for epilepsy prevention.

Effectiveness of pharmacological interventions for managing ADHD symptoms in individuals with autism spectrum disorder: A systematic review and meta-analysis.

OBJECTIVES: This systematic review sought to provide evidence for the effectiveness of common pharmacological interventions used for treating attention deficit hyperactivity disorder (ADHD) symptoms in the autism spectrum disorder (ASD) population, considering studies attempting to find safe and effective drugs. METHODS: We searched for randomized controlled trials describing the effectiveness and/or safety profile of pharmacological interventions for treating ASD and ADHD or ASD with ADHD symptoms using three bibliographic databases: PubMed, Cochrane Library, and Embase. We have chosen ADHD symptoms measured by any clinical scale as the primary outcome. As additional outcomes, we have used other symptoms of aberrant behavior measured by the aberrant behavior checklist, satisfaction with treatment, and peer satisfaction. RESULTS: Twenty-two publications met the inclusion criteria for the systematic review and eight for the meta-analysis. In our investigation, we found a few articles using clonidine, modafinil, and bupropion as interventions when compared to methylphenidate (MPH). Our meta-analysis showed that MPH had positive changes compared to placebo in symptoms such as hyperactivity, irritability, or inattention. However, no effect was found in stereotyped symptoms, and our data's quantitative analysis revealed a large effect of MPH-induced adverse effects on the dropout rate. On the other hand, atomoxetine initiation had positive effects when compared to placebo on symptoms of hyperactivity and inattention. We have found no effect of atomoxetine on stereotypes or irritability. Furthermore, atomoxetine did not influence side effects that caused dropouts from studies. CONCLUSION: Our results indicated that atomoxetine has a modest effect on hyperactivity and inattention symptoms, with a relatively benign profile of side effects. MPH appears to be effective in handling hyperactivity, inattention, and irritability symptoms. However, our results on atomoxetine revealed increased dropouts due to adverse effects when compared to MPH or placebo. Evidence for other substances such as guanfacine, clonidine, bupropion, or modafinil is either preliminary or nonexistent.

Mechanistic perspective on the actions of vitamin a in autism spectrum disorder etiology.

Vitamin A (VA) has many functions in the body, some of which are key for the development and functioning of the nervous system, while some others might indirectly influence neural function. Both hypovitaminosis and hypervitaminosis A can lead to clinical manifestations of concern for individuals and for general global health. Scientific evidence on the link between VA and autism spectrum disorder (ASD) is growing, with some clinical studies and accumulating results obtained from basic research using cellular and animal models. Remarkably, it has been shown that VA deficiency can exacerbate autistic symptomatology. In turn, VA supplementation has been shown to be able to improve autistic symptomatology in selected groups of individuals with ASD. However, it is important to recognize that ASD is a highly heterogeneous condition. Therefore, it is important to clarify how and when VA supplementation can be of benefit for affected individuals. Here we delve into the relationship between VA and ASD, discussing clinical observations and mechanistic insights obtained from research on selected autistic syndromes and laboratory models to advance in defining how the VA signaling pathway can be exploited for treatment of ASD.

Neuropsychological profile in tuberous sclerosis complex: a study of clinical and cognitive variables in a cohort from Brazil.

BACKGROUND: Tuberous sclerosis complex (TSC) is an autosomal dominant genetic disorder with a wide clinical, cognitive, and behavioral expressivity. OBJECTIVE: To assess the neuropsychological profile of individuals clinically diagnosed with TSC and the factors that could significantly impact their cognitive development. METHODS: A total of 62 individuals with ages ranging from 3 to 38 years were followed up in a tertiary attention hospital in Southern Brazil, and they were assessed using a standard battery and the Vineland Adaptive Behavior Scales, when intellectual disability was observed. RESULTS: History of epilepsy was found in 56 participants (90.3%), and 31 (50%) presented an intellectual disability. Among the other half of TSC individuals without intellectual disability, 8 (12.9%) presented borderline classification, 20 (32.2%) presented average scores, and 3 (4.8%) were above average. In total, 17 participants (27.4%) fulfilled the diagnostic criteria for autism spectrum disorder. The results of the multiple linear regression analysis suggested that seizures, age at diagnosis, visual perception, and general attention significantly impact cognitive performance indexes. CONCLUSION: The present study suggests that the occurrence of epileptic seizures and older age at diagnosis contribute to higher impairment in the domains of cognitive development, underlining the importance of early diagnosis and the prevention of epileptic seizures or their rapid control. The development of attentional skills, visual perception, and executive functions must be followed up.

ANTECEDENTES: O complexo da esclerose tuberosa (CET) é uma doença genética autossômica dominante com ampla expressividade clínica, cognitiva e comportamental. OBJETIVO: Avaliar o perfil neuropsicológico de indivíduos com diagnóstico clínico de CET e os fatores que poderiam impactar significativamente o seu desenvolvimento cognitivo. MéTODOS: Ao todo, 62 indivíduos com idades entre 3 e 38 anos foram acompanhados em um hospital terciário do Sul do Brasil e avaliados por meio de uma bateria padrão e das Escalas de Comportamento Adaptativo Vineland, quando observada deficiência intelectual. RESULTADOS: Encontrou-se histórico de epilepsia em 56 participantes (90,3%) e de deficiência intelectual em 31 (50%). Quanto à outra metade dos indivíduos com CET sem deficiência intelectual, 8 (12,9%) apresentaram classificação limítrofe, 20 (32,2%) apresentaram pontuações médias e 3 (4,8%) estavam acima da média. No total, 17 participantes (27,4%) preenchiam os critérios diagnósticos para o transtorno do espectro autista. Os resultados da análise de regressão linear múltipla sugeriram que as crises epilépticas, a idade ao diagnóstico, a percepção visual e a atenção geral impactam significativamente os índices de desempenho cognitivo. CONCLUSãO: Este estudo sugere que a ocorrência de crises epilépticas e a maior idade ao diagnóstico contribuem para um maior comprometimento nos domínios do desenvolvimento cognitivo, e destaca-se a importância do diagnóstico precoce e da prevenção das crises epilépticas ou do seu rápido controle. O desenvolvimento de habilidades de atenção, percepção visual e funções executivas deve ser acompanhado.

Disfagia no Transtorno do Espectro Autista (TEA): uma revisão integrativa / Dysphagia in Autism Spectrum Disorder (ASD): An integrative review / Disfagia en el trastorno del espectro autista (TEA): una revisión integradora

Introdução: O Transtorno do Espectro Autista (TEA) é um distúrbio do neurodesenvolvimento caracterizado por déficits na comunicação social, alterações de sensibilidade e dificuldades alimentares.Objetivo: Realizar uma revisão integrativa das alterações de deglutição em indivíduos com TEA.Métodos: A pesquisa foi realizada por meio de uma busca por artigos nacionais e internacionais, utilizando descritores para a pesquisa, bem como critérios de inclusão e exclusão para a seleção da amostra final. A estratégia PPOT foi utilizada para definir critérios de elegibilidade, incluindo população (crianças e adultos), preditor (diagnóstico de TEA), desfecho (relato ou diagnóstico de disfagia oral, faríngea ou esofágica) e tipo de estudo (estudos observatórios). A busca foi realizada no período de junho a agosto de 2023, nas bases de dados: Pubmed, Scopus, Embase e Google Scholar. Resultados: Foram selecionados dez estudos com pacientes diagnosticados com TEA que relataram sintomas de disfagia orofaríngea e esofágica, além de queixas sobre ingestão alimentar. Os estudos sugerem que crianças com TEA podem apresentar algum problema de disfunções motoras orais, frequência alimentar inadequada, padrões alimentares obsessivos, apresentação específica de determinados alimentos, seletividade alimentar e dificuldades de processamento sensorial. Conclusão: Conclui-se que não há evidências científicas robustas sobre a presença de disfagia em pacientes com TEA. (AU)

Introduction: Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder characterized by deficits in social communication, changes in sensitivity and eating difficulties. Objective: To carry out an integrative review of swallowing changes in individuals with ASD. Methods: The research was carried out through a search for national and international articles, using descriptors for the research, as well as inclusion and exclusion criteria for selecting the final sample. The PPOT strategy was used to define eligibility criteria, including population (children and adults), predictor (ASD diagnosis), outcome (report or diagnosis of dysphagia oral, pharyngeal or esophageal), and study type (observatory studies). The search was carried out from June to August 2023, in the databases: Pubmed, Scopus, Embase and Google Scholar. Results: Ten studies were selected with patients diagnosed with ASD who reported symptoms of oropharyngeal and esophageal dysphagia, in addition to complaints about food intake. Studies suggest that children with ASD may present problems with oral motor dysfunction, inadequate eating frequency, obsessive eating patterns, specific presentation of certain foods, food selectivity and sensory processing difficulties. Conclusion: It is concluded that there is no robust scientific evidence about the presence of dysphagia in patients with ASD. (AU)

Introducción: El Trastorno del Espectro Autista (TEA) es un trastorno del neurodesarrollo caracterizado por déficits en la comunicación social, cambios en la sensibilidad y dificultades alimentarias. Objetivo: Realizar una revisión integradora de los cambios en la deglución en individuos con TEA. Métodos: La investigación se realizó mediante una búsqueda de artículos nacionales e internacionales, utilizando descriptores para la investigación, así como criterios de inclusión y exclusión para la selección de la muestra final. La estrategia PPOT se utilizó para definir los criterios de elegibilidad, incluida la población (niños y adultos), el predictor (diagnóstico de TEA), el resultado (informe o diagnóstico de enfermedad oral, faríngea o esofágica) y el tipo de estudio (estudios observatorios). La búsqueda se realizó de junio a agosto de 2023, en las bases de datos: Pubmed, Scopus, Embase y Google Scholar. Resultados: Se seleccionaron diez estudios con pacientes diagnosticados de TEA que refirieron síntomas de disfagia orofaríngea y esofágica, además de quejas sobre la ingesta de alimentos. Los estudios sugieren que los niños con TEA pueden presentar problemas de disfunción motora oral, frecuencia inadecuada de alimentación, patrones alimentarios obsesivos, presentación específica de ciertos alimentos, selectividad alimentaria y dificultades en el procesamiento sensorial. Conclusión: Se concluye que no existe evidencia científica robusta sobre la presencia de disfagia en pacientes con TEA. (AU)

Low-pass whole genome sequencing as a cost-effective alternative to chromosomal microarray analysis for low- and middle-income countries.

Low-pass whole genome sequencing (LP-WGS) has been applied as alternative method to detect copy number variants (CNVs) in the clinical setting. Compared with chromosomal microarray analysis (CMA), the sequencing-based approach provides a similar resolution of CNV detection at a lower cost. In this study, we assessed the efficiency and reliability of LP-WGS as a more affordable alternative to CMA. A total of 1363 patients with unexplained neurodevelopmental delay/intellectual disability, autism spectrum disorders, and/or multiple congenital anomalies were enrolled. Those patients were referred from 15 nonprofit organizations and university centers located in different states in Brazil. The analysis of LP-WGS at 1x coverage (>50kb) revealed a positive testing result in 22% of the cases (304/1363), in which 219 and 85 correspond to pathogenic/likely pathogenic (P/LP) CNVs and variants of uncertain significance (VUS), respectively. The 16% (219/1363) diagnostic yield observed in our cohort is comparable to the 15%-20% reported for CMA in the literature. The use of commercial software, as demonstrated in this study, simplifies the implementation of the test in clinical settings. Particularly for countries like Brazil, where the cost of CMA presents a substantial barrier to most of the population, LP-WGS emerges as a cost-effective alternative for investigating copy number changes in cytogenetics.