Immunological Dysfunction in Autism Spectrum Disorder: A Potential Target for Therapy.

Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder with an unknown etiology and currently few effective therapies. Immune system alterations have being demonstrated in ASD, both in humans and via animal models; immune imbalance thus arises as a possible pathway for drug intervention. In this review, the studies were classified into 2 major groups: (1) clinical research whose authors classify therapies with primary anti-inflammatory and immunomodulatory actions, making use of: sulforaphane, celecoxib, lenalidomide, pentoxifylline, spironolactone, flavonoid luteolin, corticosteroids, oral immunoglobulin, intravenous immunoglobulin, cell therapy, dialyzable lymphocyte extracts, minocycline, and pioglitazone; and (2) other ASD therapies already used or currently under study whose initial characteristics were neither anti-inflammatory nor immunomodulatory initially, but displayed a capacity for immunomodulation throughout the treatment: risperidone, vitamin D, omega-3, Ginkgo biloba, L-carnosine, N-acetylcysteine, and microbiome restoration. These studies used various data acquisition methodologies. Questions arose such the need for randomized and placebo-controlled studies with greater numbers of participants as well as the use of biomarkers to refine the treatment of autistic subjects.

The effect of ketogenic diet in an animal model of autism induced by prenatal exposure to valproic acid.

OBJECTIVES: Autism spectrum disorder (ASD) is characterized by impairments in social interaction and communication, and by restricted repetitive behaviors and interests. Its etiology is still unknown, but different environmental factors during pregnancy, such as exposure to valproic acid (VPA), are associated with high incidence of ASD in children. In this context, prenatal exposure to VPA in rodents has been used as a reliable model of ASD. Ketogenic diet (KD) is an alternative therapeutic option for refractory epilepsy; however, the effects of this approach in ASD-like behavior need to be evaluated. We conducted a behavioral assessment of the effects of KD in the VPA model of autism. METHODS: Pregnant animals received a single-intraperitoneal injection of 600 mg/kg VPA, and their offspring were separated into four groups: (1) control group with standard diet (C-SD), (2) control group with ketogenic diet (C-KD), (3) VPA group with standard diet (VPA-SD), and (4) VPA group with ketogenic diet (VPA-KD). RESULTS: When compared with the control group, VPA animals presented increased social impairment, repetitive behavior and higher nociceptive threshold. Interestingly, the VPA group fed with KD presented improvements in social behavior. These mice displayed higher scores in sociability index and social novelty index when compared with the SD-fed VPA mice. DISCUSSION: VPA mice chronically exposed to a KD presented behavioral improvements; however, the mechanism by which KD improves ASD-like features needs to be further investigated. In conclusion, the present study reinforces the potential use of KD as a treatment for the core deficits of ASD.

HLA-G*14 bp indel variant in autism spectrum disorder in a population from southern Brazil.

Altered immune response during pregnancy has been associated with ASD susceptibility. HLA-G is expressed by the trophoblast at the maternal/fetal interface and induces allogenic tolerance toward the fetus. A 14-bp insertion in the HLA-G 3'UTR (rs371194629) was associated with reduced levels of HLA-G. We aimed to assess the influence of the HLA-G*14 bp indel variant in ASD susceptibility and symptomatology in a Brazilian admixed sample. The insertion genotype (14 bp+/14 bp+) was firstly associated with hetero aggression, but statistical significance was lost after correction (p = 0.035, pcorrected = 0.35). No association between the HLA-G variant and susceptibility to ASD or differential clinical manifestations were observed.

Exploring potential impacts of pregnancy-related maternal immune activation and extracellular vesicles on immune alterations observed in autism spectrum disorder.

Autism Spectrum Disorder (ASD) is a set of neurodevelopmental disorders usually observed in early life, with impacts on behavioral and social skills. Incidence of ASD has been dramatically increasing worldwide, possibly due to increase in awareness/diagnosis as well as to genetic and environmental triggers. Currently, it is estimated that ∼1% of the world population presents ASD symptoms. In addition to its genetic background, environmental and immune-related factors also influence the ASD etiology. In this context, maternal immune activation (MIA) has recently been suggested as a component potentially involved in ASD development. In addition, extracellular vesicles (EVs) are abundant at the maternal-fetal interface and are actively involved in the immunoregulation required for a healthy pregnancy. Considering that alterations in concentration and content of EVs have also been associated with ASD, this article raises a debate about the potential roles of EVs in the processes surrounding MIA. This represents the major differential of the present review compared to other ASD studies. To support the suggested correlations and hypotheses, findings regarding the roles of EVs during pregnancy and potential influences on ASD are discussed, along with a review and update concerning the participation of infections, cytokine unbalances, overweight and obesity, maternal anti-fetal brain antibodies, maternal fever, gestational diabetes, preeclampsia, labor type and microbiota unbalances in MIA and ASD.

Association between NKG2/KLR gene variants and epilepsy in Autism Spectrum Disorder.

Autism Spectrum Disorder (ASD) is a set of neurodevelopmental disorders mainly characterized by repetitive, restrictive and stereotypical behaviors, and impaired communication skills. Several lines of evidence indicate that alterations of the immune system account for ASD development, including the presence of brain-reactive antibodies, abnormal T cell activation, altered cytokine levels in brain, cerebrospinal fluid and peripheral blood circulation, increased levels of circulating monocytes, and dysregulation in Natural Killer (NK) cells activity. Regarding NK cells, a lower cytotoxic activity, a higher level of activation and an increased number of these cells in individuals with ASD have been described. In 2019, a study showed that NK cells derived from patients with ASD show a characteristic pattern of NKG2C overexpression, highlighting the importance of the NK cell pathway in ASD. In fact, the study of genes related to NK cell activity has proven to be an excellent research target, both in terms of susceptibility as well as a marker for the different clinical manifestations observed in ASD individuals. Here, we evaluated the influence of KLRC2 gene deletion as well as KLRK1 rs1049174 and rs2255336 variants in a cohort of 185 children diagnosed with ASD and their respective biological parents in southern Brazil. Of note, this is the first study concerning genetic variants of the KLRC2 and KLRK1 genes in an ASD sample. The KLRC2 gene deletion (p = 0.001; pc = 0.009), KLRK1 rs1049174 (p = 0.005; pc = 0.045) and KLRK1 rs2255336 (p = 0.001; pc = 0.009) were associated with epilepsy in ASD patients. The results indicate that KLRC2 deletion, KLRK1 rs2255336, and KLRK1 rs1049174 could be involved in epilepsy manifestation in ASD patients, possibly impacting the NK dysregulation already described in ASD and epileptic patients.

Cortical auditory-evoked potential as a biomarker of central auditory maturation in term and preterm infants during the first 3 months.

OBJECTIVES: To analyze central auditory maturation in term and preterm infants during the first 3 months of life by comparing the latency and amplitude of cortical auditory-evoked potential at different frequencies. METHODS: In this study, 17 term and 18 preterm infants were examined; all had tested positive on the neonatal hearing screening test. Cortical auditory potential was investigated during the first and third months of life. The response of the cortical auditory-evoked potential was investigated at frequencies of 500, 1000, 2000, and 4000 Hz. The latency and amplitude of the cortical response were automatically detected and manually analyzed by three researchers with experience in electrophysiology. The results were compared using analysis of variance and the Bonferroni test. A significance level of 5% was used for all analyses. RESULTS: Latency values of cortical auditory-evoked potential in the first month of birth were significantly higher than those in the third month, and latency values of the preterm group were higher than those of the term group, regardless of the frequency and time of evaluation. In general, the latency of the cortical auditory-evoked potential was higher at high frequencies. Amplitude values in the third month of life were significantly higher than those in the first month for term and preterm infants. CONCLUSION: Central auditory maturation was observed in both groups but with different results between those born at term and preterm, with latencies of cortical auditory-evoked potential higher for the preterm group and at high frequencies.

Central auditory processing: behavioral and electrophysiological assessment of children and adolescents diagnosed with stroke.

INTRODUCTION: Central auditory processing refers to the efficiency and effectiveness with which the central nervous system uses auditory information: it may be altered in neurological disorders and brain injuries, such as strokes. However, despite evidence of probable alterations in the pediatric population, functional abilities and post-stroke limitations are still not well documented in the literature. OBJECTIVE: To analyze the findings of the electrophysiological and behavioral evaluations of central auditory processing of children and adolescents diagnosed with stroke from a reference outpatient clinic, as well as to investigate possible associations with the variables: type and location of the stroke and age group. METHODS: The present study is characterized as comparative cross-sectional. The sample, for convenience, included individuals aged 7-18 years divided into two groups: study group, composed of individuals with a diagnosis of stroke, and control group, composed of individuals with typical development. The evaluation consisted of the following procedures: anamnesis, basic audiological evaluation, behavioral evaluation of the auditory processing disorder (dichotic digit test, dichotic consonant-vowel, synthetic sentence identification/pediatric speech intelligibility, gaps in noise, pitch pattern sequence, masking level difference), and electrophysiological evaluation (P300 and mismatch negativity). RESULTS: Nineteen children and adolescents were included in the study group. The control group was composed of 19 children and adolescents with typical development. In the comparison between the groups, a worse performance is observed for the study group in all the evaluated tests, behavioral and electrophysiological. In the behavioral evaluation of central auditory processing, there was a statistical difference for all tests, except for masking level difference and dichotic digit test, binaural separation step on the left. In the electrophysiological evaluation, there was a statistical difference in the latency of mismatch negativity and P300. No associations were found between the behavioral and electrophysiological findings and the location of the stroke and age group variables. CONCLUSION: Children and adolescents diagnosed with stroke present a worse performance in the electrophysiological and behavioral evaluations of central auditory processing when compared to a control group.

Hyperbilirubinemia impact on newborn hearing: a literature review.

The increase in bilirubin levels in newborns can cause toxic effects on the auditory system, which can lead to hearing loss. This review aimed to verify the impact of hyperbilirubinemia in the hearing of newborns, relating audiological findings to serum levels of bilirubin. A literature review was conducted during October 2017, using the terms "hyperbilirubinemia", "jaundice", "infant", "newborn" and "hearing loss", on databases CAPES journals, MEDLINE and BIREME (SciELO, BBO). 827 studies were identified and 59 were selected for full-text reading, resulting in the selection of seven articles that met the inclusion criteria and were considered relevant to the sample of this study. All the reviewed studies performed brainstem auditory evoked potential as the main test for audiological evaluation. Changes in the audiological findings of neonates with hyperbilirubinemia were observed in all studies. There was no consensus on the serum bilirubin levels that may cause auditory changes; however, the relationship between hearing disorders and blood levels of bilirubin was positive. We identify the need to establish reference values for bilirubin levels considered critical for the occurrence of hearing disorders as well as the audiological follow-up of neonates with hyperbilirubinemia.

Cortical auditory evoked potential in assessment of neonates: a study about minimum level of responses in term and preterm newborns.

INTRODUCTION: The study of the threshold level of cortical auditory response in adults has been investigated in previous studies. Due to maturational issues, little is known about these responses in neonates. Technological advances with automatic analysis devices now allow investigation in specific populations. Thus, new studies are needed to establish the feasibility of using this auditory potential to identify the lowest levels of responses in children. OBJECTIVE: Verify and compare latency and amplitude in 80dBnNA and the minimum level of cortical auditory response in term and preterm neonates. METHODS: A cross-sectional, comparative study involving 59 neonates, 35 full-term births and 24 preterm births, with positive results in the Neonatal Hearing Screening. The Hearlab system was used to investigate the P1i auditory potential with tone burst stimulus at frequencies of 500, 1000, 2000 and 4000Hz. The minimum response level search ranged from 80 to 0dBNA and was detected automatically. The results were compared between groups, evaluating the latency and amplitude in 80dBNA and the minimum level of cortical auditory response. RESULTS: The mean values obtained for the minimum level of cortical auditory response in term group were 26±8.81; 26.14±6.97; 29±7.65 and 29.43±7.04dBNA and for preterm neonates of 31.96±10.41; 34.13±11.34; 33.64±11.03 and 37.73±11.92dBNA, for the frequencies of 500, 1000, 2000 and 4000Hz, respectively. There was a difference between groups for the latency of P1i at 4000Hz and the minimum response levels at 500, 1000 and 4000Hz, with higher values for preterm infants. CONCLUSION: It was possible to obtain latency and amplitude values at 80dBnNA and the minimum level of cortical response in term and preterm newborns, with different results between groups, with higher values in those born preterm.

The effect of the "K" technique on levels of anxiety and salivar cortisol in adolescents / O efeito da técnica "K" nos níveis de ansiedade e cortisol salivar em adolescentes / El efecto de la técnica "K" sobre la ansiedad y los niveles de cortisol salivales en adolescentes

This research presents theoretical arguments of a new approach called Technique "K," which aims to reduce student's anxiety before a cognitive challenge. Through a randomized, controlled clinical trial, we evaluate the Beck Anxiety Inventory and salivary cortisol. We compared the results in the last year of high school, who were facing school tests, before and after the application of the "K" technique (intervention group) and placebo (control group). Statistical analyses consisted of using the Chisquare, Spearman and the Wilcoxon test. The principal component analysis observed in the case group, - 10.50 (-18.25; -4.75), was statistically higher than the control group, -6.00 (-8.75; -1.25). It is not possible to identify statistical significance (p = 0.462) in the variation of salivary cortisol concentration. The results suggest the effectiveness of the "K" technique in managing anxiety in high school students. Although, future research is needed to extend the preliminary data obtained in this study

Esta pesquisa apresenta argumentos teóricos de uma nova abordagem denominada Técnica "K", visando reduzir a ansiedade do aluno diante de um desafio cognitivo. Por meio de um ensaio clínico randomizado e controlado, avaliamos o Inventário de Ansiedade de Beck e o cortisol salivar. Comparamos os resultados dos alunos, que estavam enfrentando provas escolares, antes e após a aplicação da técnica "K" (grupo intervenção) e placebo (grupo controle). As análises estatísticas consistiram na utilização do Qui-quadrado, Spearman e teste de Wilcoxon. A análise de componentes principais observada no grupo caso, -10,50 (-18,25; -4,75), foi estatisticamente superior ao grupo controle, -6,00 (-8,75; -1,25). Não é possível identificar significância estatística (p = 0,462) na variação da concentração de cortisol salivar. Os resultados sugerem a eficácia da técnica "K" no manejo da ansiedade em estudantes do ensino médio. No entanto, pesquisas futuras são necessárias para estender os dados preliminares obtidos neste estudo

Esta investigación presenta argumentos teóricos para un nuevo enfoque denominado Técnica "K", con el objetivo de reducir la ansiedad de los estudiantes frente a un desafío cognitivo. A través de un ensayo clínico aleatorizado y controlado, evaluamos el Inventario de Ansiedad de Beck y el cortisol salival. Comparamos los resultados de los estudiantes, que se enfrentaban a pruebas escolares, antes y después de la aplicación de la técnica "K" (grupo de intervención) y placebo (grupo control). Los análisis estadísticos consistieron en utilizar la prueba de Chicuadrado, Spearman y Wilcoxon. El análisis de componentes principales observado en el grupo de casos, -10,50 (-18,25; -4,75), fue estadísticamente superior al grupo control, -6,00 (-8,75; -1,25). No es posible identificar significación estadística (p = 0,462) en la variación de la concentración de cortisol salival. Los resultados sugieren la efectividad de la técnica "K" en el manejo de la ansiedad en estudiantes de secundaria. Sin embargo, se necesitan futuras investigaciones para ampliar los datos preliminares obtenidos en este estudio

Air and Bone Conduction Frequency-specific Auditory Brainstem Response in Children with Agenesis of the External Auditory Canal.

Introduction The tone-evoked auditory brainstem responses (tone-ABR) enable the differential diagnosis in the evaluation of children until 12 months of age, including those with external and/or middle ear malformations. The use of auditory stimuli with frequency specificity by air and bone conduction allows characterization of hearing profile. Objective The objective of our study was to compare the results obtained in tone-ABR by air and bone conduction in children until 12 months, with agenesis of the external auditory canal. Method The study was cross-sectional, observational, individual, and contemporary. We conducted the research with tone-ABR by air and bone conduction in the frequencies of 500 Hz and 2000 Hz in 32 children, 23 boys, from one to 12 months old, with agenesis of the external auditory canal. Results The tone-ABR thresholds were significantly elevated for air conduction in the frequencies of 500 Hz and 2000 Hz, while the thresholds of bone conduction had normal values in both ears. We found no statistically significant difference between genders and ears for most of the comparisons. Conclusion The thresholds obtained by bone conduction did not alter the thresholds in children with conductive hearing loss. However, the conductive hearing loss alter all thresholds by air conduction. The tone-ABR by bone conduction is an important tool for assessing cochlear integrity in children with agenesis of the external auditory canal under 12 months.

A Placebo-Controlled Crossover Trial of Gastrin-Releasing Peptide in Childhood Autism.

OBJECTIVES: The aim of this study was to evaluate the efficacy, safety, and tolerability of gastrin-releasing peptide (GRP) compared with placebo in autism spectrum disorder symptoms. METHODOLOGY: This is a randomized, double-blind, placebo-controlled crossover trial using GRP 160 pmol/kg for 4 consecutive days in 10 children with autism. Outcomes were measured by the Aberrant Behavior Checklist (ABC) scale. RESULTS: All participants were boys, aged between 4 and 9 years. There was a reduction in the scores of the ABC range and its subscales after use GRP and placebo. The reduction was more prominent with GRP, particularly in the subscale "hyperactivity and noncompliance," but there was no statistical difference between the results (P = 0.334). After a week of infusion, 5 children showed improvement of 25% or greater in the total score of the ABC scale with GRP use and 2 with placebo use; however, there was no statistical difference (P = 0.375). There were no adverse effects, changes in vital signs, or laboratory abnormalities associated with the use of GRP. CONCLUSIONS: The results of this study, despite the small sample size, reinforce previous data on the safety of the GRP in short-term use. There is a need for further research with other designs and a larger sample size to evaluate the efficacy and safety of GRP in children with autism.

Improvement of autism spectrum disorder symptoms in three children by using gastrin-releasing peptide.

OBJECTIVE: To evaluate the safety, tolerability and potential therapeutic effects of gastrin-releasing peptide in three children with autistic spectrum disorder. METHODS: Case series study with the intravenous administration of gastrin-releasing peptide in the dose of 160pmol/kg for four consecutive days. To evaluate the results, parental impressions the Childhood Autism Rating Scale (CARS) and the Clinical Global Impression (CGI) Scale. Each child underwent a new peptide cycle after two weeks. The children were followed for four weeks after the end of the infusions. RESULTS: The gastrin-releasing peptide was well tolerated and no child had adverse effects. Two children had improved social interaction, with a slight improvement in joint attention and the interaction initiatives. Two showed reduction of stereotypes and improvement in verbal language. One child lost his compulsion to bathe, an effect that lasted two weeks after each infusion cycle. Average reduction in CARS score was 2.8 points. CGI was "minimally better" in two children and "much better" in one. CONCLUSIONS: This study suggests that the gastrin-releasing peptide is safe and may be effective in improving key symptoms of autism spectrum disorder, but its results should be interpreted with caution. Controlled clinical trials-randomized, double-blinded, and with more children-are needed to better evaluate the possible therapeutic effects of gastrin-releasing peptide in autism.

Cortical auditory-evoked potential as a biomarker of central auditory maturation in term and preterm infants during the first 3 months

OBJECTIVES: To analyze central auditory maturation in term and preterm infants during the first 3 months of life by comparing the latency and amplitude of cortical auditory-evoked potential at different frequencies. METHODS: In this study, 17 term and 18 preterm infants were examined; all had tested positive on the neonatal hearing screening test. Cortical auditory potential was investigated during the first and third months of life. The response of the cortical auditory-evoked potential was investigated at frequencies of 500, 1000, 2000, and 4000 Hz. The latency and amplitude of the cortical response were automatically detected and manually analyzed by three researchers with experience in electrophysiology. The results were compared using analysis of variance and the Bonferroni test. A significance level of 5% was used for all analyses. RESULTS: Latency values of cortical auditory-evoked potential in the first month of birth were significantly higher than those in the third month, and latency values of the preterm group were higher than those of the term group, regardless of the frequency and time of evaluation. In general, the latency of the cortical auditory-evoked potential was higher at high frequencies. Amplitude values in the third month of life were significantly higher than those in the first month for term and preterm infants. CONCLUSION: Central auditory maturation was observed in both groups but with different results between those born at term and preterm, with latencies of cortical auditory-evoked potential higher for the preterm group and at high frequencies.

Hyperbilirubinemia impact on newborn hearing: a literature review

SUMMARY The increase in bilirubin levels in newborns can cause toxic effects on the auditory system, which can lead to hearing loss. This review aimed to verify the impact of hyperbilirubinemia in the hearing of newborns, relating audiological findings to serum levels of bilirubin. A literature review was conducted during October 2017, using the terms "hyperbilirubinemia", "jaundice", "infant", "newborn" and "hearing loss", on databases CAPES journals, MEDLINE and BIREME (SciELO, BBO). 827 studies were identified and 59 were selected for full-text reading, resulting in the selection of seven articles that met the inclusion criteria and were considered relevant to the sample of this study. All the reviewed studies performed brainstem auditory evoked potential as the main test for audiological evaluation. Changes in the audiological findings of neonates with hyperbilirubinemia were observed in all studies. There was no consensus on the serum bilirubin levels that may cause auditory changes; however, the relationship between hearing disorders and blood levels of bilirubin was positive. We identify the need to establish reference values for bilirubin levels considered critical for the occurrence of hearing disorders as well as the audiological follow-up of neonates with hyperbilirubinemia.

RESUMO O aumento nos níveis de bilirrubina no neonato pode provocar efeitos tóxicos no sistema auditivo, podendo levar à perda auditiva. O objetivo desta revisão foi verificar o impacto da hiperbilirrubinemia na audição de recém-nascidos, relacionando os achados audiológicos aos níveis séricos de bilirrubina. Realizou-se uma revisão sistemática de literatura durante o mês de outubro de 2017, utilizando-se os termos hyperbilirubinemia, jaundice, infant, newborn e hearing loss, nas bases de dados periódicos Capes, Medline e Bireme (SciELO, BBO). Foram identificados 827 estudos, dentre os quais 59 foram selecionados para leitura do texto na íntegra, resultando na seleção de sete artigos que atendiam aos critérios de inclusão e foram considerados relevantes para a amostra deste trabalho. Em todas as pesquisas revisadas, o potencial evocado auditivo de tronco encefálico foi o principal exame audiológico realizado. Em todos os estudos foram observadas alterações nos resultados audiológicos de neonatos com hiperbilirrubinemia. Não houve consenso quanto aos níveis séricos de bilirrubina que podem causar alterações auditivas, porém, a relação entre as alterações audiológicas e os níveis sanguíneos de bilirrubina foi positiva. Percebeu-se a necessidade de estabelecer valores de referência para os níveis de bilirrubina considerados críticos para a ocorrência de alterações audiológicas, assim como de acompanhamento audiológico dos neonatos com hiperbilirrubinemia.

HTLV-1-associated infective dermatitis and probable HTLV-1- associated myelopathy in an adolescent female.

Human T cell lymphotropic virus type 1 (HTLV-1)-associated infective dermatitis (ID) is a chronic, severe and recurrent eczema occurring during childhood in patients vertically infected with HTLV-1. HTLV-1-associated myelopathy/tropical spastic paraparesia (HAM/ TSP) is slow and progressive. We report the case of an adolescent female from a non-endemic area for HTLV-1 who presents ID and, most likely, associated HAM/TSP.

Cortical auditory evoked potential in assessment of neonates: a study about minimum level of responses in term and preterm newborns / Potencial evocado auditivo cortical na avaliac¸ão de neonatos: um estudo sobre o nível mínimo de respostas em nascidos a termo e pré-termos

Abstract Introduction: The study of the threshold level of cortical auditory response in adults has been investigated in previous studies. Due to maturational issues, little is known about these responses in neonates. Technological advances with automatic analysis devices now allow investigation in specific populations. Thus, new studies are needed to establish the feasibility of using this auditory potential to identify the lowest levels of responses in children. Objective: Verify and compare latency and amplitude in 80 dBnNA and the minimum level of cortical auditory response in term and preterm neonates. Methods: A cross-sectional, comparative study involving 59 neonates, 35 full-term births and 24 preterm births, with positive results in the Neonatal Hearing Screening. The Hearlab system was used to investigate the P1i auditory potential with tone burst stimulus at frequencies of 500, 1000, 2000 and 4000 Hz. The minimum response level search ranged from 80 to 0 dBNA and was detected automatically. The results were compared between groups, evaluating the latency and amplitude in 80 dBNA and the minimum level of cortical auditory response. Results: The mean values obtained for the minimum level of cortical auditory response in term group were 26 ± 8.81; 26.14 ± 6.97; 29 ± 7.65 and 29.43 ± 7.04 dBNA and for preterm neonates of 31.96 ± 10.41; 34.13 ± 11.34; 33.64 ± 11.03 and 37.73 ± 11.92 dBNA, for the frequencies of 500, 1000, 2000 and 4000 Hz, respectively. There was a difference between groups for the latency of P1i at 4000 Hz and the minimum response levels at 500, 1000 and 4000 Hz, with higher values for preterm infants. Conclusion: It was possible to obtain latency and amplitude values at 80 dBnNA and the minimum level of cortical response in term and preterm newborns, with different results between groups, with higher values in those born preterm.

Resumo Introdução: A investigação do nível mínimo de resposta auditiva cortical tem sido alvo de diferentes estudos em adultos. Devido a questões de maturação, pouco se sabe sobre essas respostas em recém-nascidos. Com o avanço tecnológico, dispositivos de análise automática surgiram com o objetivo de retomar essa avaliação em populações específicas. Assim, novos estudos são necessários para verificar a viabilidade do uso desse potencial auditivo na obtenção de níveis mínimos de respostas na criança. Objetivo: Verificar e comparar latência e amplitude em 80 dBnNA e o nível mínimo de resposta auditiva cortical em recém-nascidos a termo e pré-termo. Método: Estudo transversal, comparativo, envolvendo 59 neonatos, 35 nascidos a termo e 24 pré-termos, com resultados positivos na triagem auditiva neonatal. O sistema Hearlab foi utilizado para investigar o potencial auditivo P1i com estímulo tone burst nas frequências de 500, 1000, 2000 e 4000 Hz. A busca do nível mínimo de resposta variou de 80 a 0 dBNA e foi detectado automaticamente. Os resultados foram comparados entre os grupos, avaliando a latência e amplitude em 80 dBNA e o nível mínimo de resposta auditiva cortical. Resultados: Os valores médios obtidos para o nível mínimo de resposta auditiva cortical no grupo nascido a termo foram 26 ± 8,81; 26,14 ± 6,97; 29 ± 7,65 e 29,43 ± 7,04 dBNA e para recém-nascidos pré-termos foram de 31,96 ± 10,41; 34,13 ± 11,34; 33,64 ± 11,03 e 37,73 ± 11,92 dBNA, para as frequências de 500, 1000, 2000 e 4000 Hz, respectivamente. Houve diferenc¸a entre os grupos para a latência de P1i em 4000 Hz e os níveis mínimos de resposta em 500, 1000 e 4000 Hz, com valores maiores em Pré-termos. Conclusão: Foi possível obter valores de latência e amplitude em 80 dBnNA e o nível mínimo de resposta cortical em recém-nascidos a termo e Pré-termos, com resultados diferentes entre osgrupos, com valores maiores em pré-termos.

Aquisição fonológica em pré-escolares e deficiência de ferro: um estudo populacional / Phonological acquisition in pre-school children and iron deficiency: a population study / Adquisición fonológica en preescolares y deficiencia de hierro: un estudio populacional

Introdução ­ Esta pesquisa teve o objetivo de analisar a aquisição fonológica e sua relação com dados demográficos e a deficiência de ferro em pré-escolares da cidade de Vicente Dutra-RS. Método­ Foi realizado estudo transversal, utilizando dados de hemograma (hemoglobina, ferritina e saturação transferrina) e dados sobre a aquisição da linguagem oral e da escrita numa população de 51 crianças (26 meninas, 51%), com 5,3±0,3 anos de idade. Resultados ­ Não foi encontrada associação da deficiência de ferro com aquisição da linguagem oral e escrita. Contudo, foi observada associação entre as variáveis aquisição fonológica e hipótese de escrita (valor sonoro), p=0,006, e aquisição fonológica e desvios fonéticos (p=0,012). Conclusões ­ Os dados encontrados nesta pesquisa transversal não sugerem relação entre linguagem e deficiência de ferro; contudo, amostras maiores em estudos longitudinais seriam interessantes para melhor compreensão dos achados.

Introducción - Esta investigación tuvo el objetivo de analizar la adquisición fonológica y su relación con datos demográficos y la deficiencia de hierro en preescolares de la ciudad de Vicente Dutra-RS. Método ­ Se realizó un estudio transversal, utilizando datos de hemograma (hemoglobina, ferritina y saturación transferrina) y datos sobre la adquisición del lenguaje oral y de la escritura en una población de 51 niños (26 niñas, 51%), con 5,3 ± 0, 3 años de edad. Resultados - No se encontró asociación de la deficiencia de hierro con adquisición del lenguaje oral y escrito. Sin embargo, se observó asociación entre las variables de adquisición fonológica y hipótesis de escritura (valor sonoro), p = 0,006, y adquisición fonológica y desvíos fonéticos (p = 0,012). Conclusiones - Los datos encontrados en esta investigación transversal no sugieren una relación entre el lenguaje y la deficiencia de hierro; sin embargo, muestras más grandes en estudios longitudinales serían interesantes para una mejor comprensión de los hallazgos.

Introduction - This research aimed to analyze the phonological acquisition and its relationship with demographic data and iron deficiency in preschool children from Vicente Dutra-RS. Method - It was performed a cross-sectional study, using hemogram data (hemoglobin, ferritin and transferrin saturation), and data on acquisition of oral and written language in a population of 51 children (26 girls, 51%), with 5.3±0.3 years of age. Results - It was not found an association between iron deficiency and acquisition of oral and written language. However, it was observed an association between the variables phonological acquisition and chance of writing (value), p = 0.006, and phonological acquisition and phonetic deviations (p = 0.012). Conclusions - The data found in this cross-sectional research do not suggest a relationship between language and iron deficiency; however, larger samples in longitudinal studies would be interesting for a better understanding of the findings.

[Advances in the management of neonatal hypoxia]. / Avances en el abordaje de la hipoxia neonatal.

INTRODUCTION: During the birth, physiological changes occur in virtually all organs of the child, including the central nervous system. In this transitional phase, it is possible some degree of hypoxemia, generally well tolerated by the newborn. But, if neonatal hypoxia is intense and continuous it can lead to neonatal encephalopathy, which characterizes a critical situation for the infant. The proper approach is essential to ensure a good long-term prognosis. DEVELOPMENT: We up-to-date information regarding hypoxia neonatal and review recent evidence-based medicine publications addressing its approach. CONCLUSIONS: Neonatal encephalopathy may be clinically classified into three levels of intensity. Mild cases usually have a good prognosis, moderate intensity cases have 30% chance of sequels, and severe intensity cases have more than 70% mortality and nearly all survivors have sequels. Recent advances occurred in two areas: in the diagnosis, with new EEG and MRI techniques, and in the treatment, with the advent of therapeutic hypothermia. There is the possibility of future use for stem cell therapy. The prognosis depends on the clinical classification, the neuroimaging data as well as the EEG.

TITLE: Avances en el abordaje de la hipoxia neonatal.Introduccion. Durante el nacimiento, ocurren cambios fisiologicos en practicamente todos los organos del niño, incluyendo el sistema nervioso central. En esta fase de transicion, es posible un cierto grado de hipoxemia, en general bien tolerado por el neonato. Sin embargo, si la hipoxia neonatal es muy intensa y continuada, puede instalarse una encefalopatia neonatal, lo que caracteriza una situacion critica para el recien nacido. Su abordaje adecuado es imprescindible para garantizar un buen pronostico a largo plazo. Desarrollo. Se actualizan las informaciones acerca de la hipoxia neonatal y se revisan publicaciones recientes acerca de los avances en su abordaje a traves de la medicina basada en evidencias. Conclusiones. La encefalopatia neonatal se puede clasificar desde el punto de vista clinico en tres niveles de intensidad. Usualmente, los casos leves tienen un buen pronostico, los casos de intensidad moderada tienen un 30% de posibilidad de secuelas y los de intensidad grave tienen mas del 70% de mortalidad, pero practicamente todos los supervivientes tendran secuelas. Los avances ocurrieron en dos areas: en el diagnostico, con nuevas tecnicas de EEG y RM, y en el tratamiento, con la aparicion de la hipotermia terapeutica. Existe la posibilidad de un uso futuro para la terapia con celulas madre. El pronostico depende de la clasificacion clinica, de los datos de neuroimagen y del EEG.

O impacto do acidente vascular cerebral na qualidade de vida de crianças e adolescentes / El impacto del ataque cerebrovascular en la cualidad de vida de niños y adolescentes / The impact of stroke on the quality of life of children and adolescents

RESUMO O objetivo deste estudo foi avaliar a qualidade de vida (QV) de crianças/adolescentes com diagnóstico de acidente vascular cerebral (AVC) segundo as percepções do responsável e das próprias crianças/adolescentes comparados com um grupo controle (GC). Participaram 78 sujeitos divididos em: Grupo de crianças/adolescentes que tiveram histórico de AVC (GAVC, n=39) e um Grupo de crianças/adolescentes saudáveis como Controle (GC, n=39), sendo pareados por sexo e idade. Utilizou-se de entrevista semiestruturada para descrever os aspectos sociodemográficos e do instrumento Pediatric Quality of Life Inventory (PedsQLTM 4.0) para avaliar a QV dos sujeitos no seu desenvolvimento. A mediana de idade do diagnóstico de AVC do GAVC foi sete meses, sendo que a maioria apresentou AVC isquêmico (71,8%) e hemiparesia. De acordo com os responsáveis do GAVC, a Capacidade Funcional dos seus filhos foi significativamente diferente, apresentando inferioridade em relação ao GC. Para os responsáveis também a variável escolaridade do pai manteve efeito positivo significativo nos aspectos emocionais da criança, e a variável idade da criança/adolescente e tempo do AVC >29 dias de vida apresentou efeito negativo nos aspectos escolares. Já para as crianças/adolescentes, a variável idade em que entrou na escola e gênero apresentou efeito significativo negativo no desfecho de aspectos escolares em relação ao GC. Concluímos que a percepção dos responsáveis difere da percepção da criança/adolescente em relação à capacidade funcional desta; a escolaridade do pai influenciou positivamente nos aspectos emocionais da criança, e as crianças sentem-se com um prejuízo no desempenho escolar, principalmente os meninos.

RESUMEN El objetivo de este estudio ha sido evaluar la cualidad de vida (CV) de niños/adolescentes con diagnóstico de ataque cerebrovascular (ACV), según las percepciones del responsable y de los propios niños/adolescentes comparados con un grupo control (GC). Han participado 78 sujetos divididos en: Grupo de niños/adolescentes que han tenido histórico de ACV (GACV, n=39) y un Grupo de niños/adolescentes saludables como Control (GC, n=39), siendo pareados por sexo y edad. Se ha utilizado de encuesta semiestructurada para describir los aspectos sociodemográficos y del instrumento Pediatric Quality of Life Inventory (PedsQLTM 4.0) para evaluar la CV de los sujetos en su desarrollo. El promedio de edad del diagnóstico de ACV del GACV ha sido siete meses, siendo que la gran parte ha presentado ACV isquémico (el 71,8%) y hemiparesia. De acuerdo con los responsables del GACV, la Capacidad Funcional de sus hijos ha sido significativamente, distinta, presentando inferioridad en relación al GC. Para los responsables también la variable escolaridad del padre ha mantenido el efecto positivo significativo en los aspectos emocionales del niño, y la variable edad del niño/adolescente y tiempo del ACV >29 días de vida ha presentado el efecto negativo en los aspectos escolares. Ya para los niños/adolescentes, la variable edad en que ha ingresado a la escuela y el género ha presentado efecto significativo negativo en el desfecho de aspectos escolares en relación al GC. Hemos concluido que la percepción de los responsables difiere de la percepción del niño/adolescente en relación a la capacidad funcional de esta; la escolaridad del padre ha influenciado positivamente en los aspectos emocionales del niño, y los niños se sienten con un perjuicio en el desempeño escolar, principalmente los niños.

ABSTRACT The aim of this study was to evaluate the quality of life (QoL) of children/adolescents with a diagnosis of stroke (CVA) in the eyes of the person responsible and the children / adolescents themselves compared to a control group. 78 subjects were divided into: Group of children / adolescents who had a history of stroke (GAVC, n = 39) and a group of healthy children/adolescents as Control (CG, n = 39) matched by gender and age. A semi-structured interview was used to describe the sociodemographic aspects and the Pediatric Quality of Life Inventory (PedsQLTM 4.0) to evaluate the QoL of the subjects in their development. The median age of the diagnosis of stroke was 7 months, with the majority presenting ischemic stroke (71.8%) and hemiparesis.According to those responsible for the GAVC, the Functional Capacity of their children was significantly different, presenting inferiority in relation to the CG. Also, for those in charge, the father's educational variable maintained a significant positive effect on the emotional aspects of the child, and the variable age of the child /adolescent and stroke time> 29 days of life had a negative effect on the school aspects. As for the children / adolescents, the variable age that entered school and gender had a significant negative effect on the outcome of school aspects in relation to the CG. We conclude that the view of those responsible differs from the child/adolescent's view of their functional capacity; the father's schooling positively influenced the emotional aspects of the child and the children feel a loss in school performance, especially the boys.