[Follow up of patients with developmental delay and autistic spectrum disorders]. / Evolución de los niños con retraso del desarrollo y conductas del espectro autista.

The evolution of autism symptoms during life were revised, from childhood to adulthood. Little information is available. After a search in PubMed, no more than 40 publications address this issue. The review was divided into two parts: a) how change the three main symptoms of autism change; b) how change the other autism-associated symptoms. The three main symptoms, called "Triad of Wing" (communication problems, social skills deficits, and a restricted repertoire of interests) do not change significantly during lifetime. The diagnosis of autism remains stable during lifetime, and 80% of children continue with this diagnosis in adulthood. Furthermore, it is difficult to establish first diagnostic of autism in adults. In relation to the associated symptoms, one of the earliest are sleep disturbances and one of the most prevalent is both bipolar and anxiety disorders. Sleep disturbances are age-limited and disappear easily. Bipolar disorders are usually more severe in children with autism when compared to children without autism. The mood transitions are faster in autistic children. Anxiety is usually more intense in cognitive preserved autistic patients and tends to increase with age. The two main prognostic factors for autism in adults are: a) total IQ above 70. b) functional language before 6 years of age.

Treatment of refractory neonatal seizures with topiramate.

OBJECTIVE: The objective of this study is to describe the usefulness of topiramate in refractory neonatal seizures. RESULTS: We reported the clinical off-label use of topiramate in three cases of refractory neonatal seizures of unclear origin with no response to conventional antiepileptic drugs. In all cases, the seizures were completely controlled with adding topiramate. All patients became seizure free during hospitalization and were followed by approximately 1 year after hospital discharge, with monotherapy with topiramate. COMMENTS: The clinical off-label use of topiramate in neonatal seizures is still incipient. When searching publications in this matter, only one report was identified. Because of its efficacy for both seizures and neuroprotection, topiramate could be a useful choice in refractory neonatal seizures.

Proteus syndrome associated with hemimegalencephaly and Ohtahara syndrome: report of two cases.

The authors report two cases of Brazilian children with most of the common syndromic features of Proteus syndrome, such as asymmetric overgrowth of tissues, skin abnormalities, hypotonia and mental retardation. In both patients, a refractory epilepsy, compatible with Ohtahara syndrome, as well as hemimegalencephaly, with asymmetric distribution of facial fat, were also diagnosed.

[Syndrome of cerebral non-dominant hemisphere]. / Síndromes del hemisferio no dominante.

In this review the meaning of cerebral hemispheric function is discussed with special emphasis in non-dominant cerebral hemisphere and particularly in the lesion of commissural, association, projection of white matter fibers. Clinical characteristics depend on etiology, localization, extension and particularly the period of brain development. The following are common findings in these patients: left hemiplegia, abnormal prosody and non verbal communication, anomalies visiospatial perception, organization, and social interaction. Similar symptoms are also present in some developmental disorders such as attention deficit hyperactive disorders and Asperger syndrome. We discuss seven cases of isquemic cerebrovascular accidents with the objective of demonstrating the more frequent and persistent findings in the acquired lesion. All patients had complete neurological and neuropsychological evaluation, and were followed up for more than two years. We conclude that motor sequel is less severe than cognitive and affective consequences.

[Surgical indications in pediatric epilepsy]. / Indicaciones quirúrgicas de la epilepsia en la niñez.

With the goal of presenting follow-up data from patients seen at the Refractory Epilepsy out-patient clinic of the Hospital de Clínicas de Porto Alegre (HCPA), Brazil, we reviewed the literature on childhood and adolescent epilepsy and epileptic syndromes with indication for surgical treatment. The International League Against Epilepsy's Subcommission for Pediatric Epilepsy Surgery recommends surgical evaluation for cortical dysplasia, tuberous sclerosis complex, polymicrogyria, hypothalamic hamartoma, hemispheric syndromes, Sturge-Weber, Rasmussen, Landau-Kleffner and other situations such as tumors or cerebrovascular injury. The Subcommission proposes the creation of referral centers with functional methods of evaluation, structural imaging, and a multidisciplinary team that includes neurologists, neurosurgeons, neurophysiologists, neuropediatricians, neuropsychologists, pathologists, neuroradiologists and eletroneurophysiology technicians. Creating these centers in developing countries is possible with the cooperation of other regions. Studies have shown improvement in quality of life with less frequent seizures. At HCPA, we provide evaluations and ongoing clinical management of patients with medically refractory epilepsy. Epilepsy surgery is potentially curative and is particularly useful for the pediatric population.

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 in Symptoms of Autism Spectrum Disorder in Children With the Use of Gastrin-Releasing Peptide: An Open Trial.

OBJECTIVES: The aim of this study was to determine the efficacy and tolerability of gastrin-releasing peptide (GRP) for core symptoms of autism spectrum disorder. METHODS: This is a prospective, open-label study with 160 pmol/kg of GRP tested in 10 children with autism. Outcome measures used were the Clinical Global Impressions-Improvement Scale, Aberrant Behavior Checklist (ABC), Childhood Autism Rating Scale, and Autism Diagnostic Interview-Revised. Positive response was defined as a score of 1 (very much improved) or 2 (much improved) on the Clinical Global Impressions-Improvement Scale and an improvement of 25% or greater on at least 1 subscale of ABC. RESULTS: Six (60%) of the 10 subjects responded to GRP. Improvements were observed on the ABC irritability and hyperactivity subscales in 80% of patients, and 70% exhibited improvement on the social withdrawal subscale. On the Childhood Autism Rating Scale, there was a mean reduction of 4 points (4.3 ± 2.9). Analysis of the Autism Diagnostic Interview-Revised results detected significant improvements in the domain that assesses social interaction, with a mean reduction of 2.4 points (2.4 ± 2.83). Adverse effects occurred in 3 patients. CONCLUSIONS: Gastrin-releasing peptide was safe and well tolerated by most subjects and may be effective for core symptoms of 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.

Parachute and lateral propping reactions in preterm children.

A non-controlled, prognostic cohort study was performed with the aim of establishing markers of neurological development and defining a clinical and epidemiological profile of preterm newborns at 3, 6, 9, and 12 months of gestation-corrected age in terms of parachute and lateral propping reactions. Newborns with gestational age of up to 36 weeks and 6 days, weighing 2,000 g or less at birth, were included in the study At 6 months of age, parachute and lateral propping reactions were present in 8.1% of the patients. At 9 months, the parachute reaction was present in 87.5%, and the lateral propping reaction was present in 90% of the children. It was possible to assess parachute and lateral propping reactions in preterm children in the first year of life. Alterations in trunk-limb coordination may be evidenced in the 1st year of life through postural reactions, which are maintained as prematurity markers until school age.

[Vigabatrin in the treatment of epilepsy in patients with West syndrome and tuberous sclerosis]. / Vigabatrina no tratamento da epilepsia de difícil controle em pacientes com síndrome de West e esclerose tuberosa.

PURPOSE: To report the efficacy of vigabatrin in seizures control, as well as the electroencephalographic abnormalities in children with tuberous sclerosis and West syndrome. METHOD: Retrospective study, with clinical, neuroimaging, and electroencephalographic data. RESULTS: Seven patients were followed, and the median time of follow-up was 10 years. Four of them were females and all were white. The mean age of seizures onset was 3.4 months. All patients used antiepileptic drugs associations, at least 2 drugs each therapeutic scheme, each one of the patients have used at least two different schemes. Vigabatrin as monotherapy or adjuvant was started in a mean age of seven years or 4 years after the onset of symptoms. Five from seven patients on vigabatrin became seizure free. CONCLUSION: Vigabatrin was efficient in seizures control, leading to a better prognosis.

Influence of intracranial hemorrhage and neonatal seizures on the neurological and psychomotor development of premature infants at Hospital de Clínicas de Porto Alegre, Brazil.

UNLABELLED: This study compared the results of neurodevelopmental examination at 6 months' corrected age of premature infants with neonatal seizures and/or intracranial hemorrhage and normal premature infants. There was a statistically significant correlation (p=0.000007) between intracranial hemorrhage and seizures in the group of 68 premature infants seen in the neurodevelopmental outpatient service at Hospital de Clínicas de Porto Alegre, Brazil. Intracranial hemorrhage was significantly associated with multiparity (p=0.02). The neurodevelopmental examination at 6 months' corrected age revealed that patients who suffered neonatal intracranial hemorrhage and/or seizures had inappropriate muscle tone, strength and reflexes, as well as delay in head control. CONCLUSION: We compared the results of neurodevelopmental examinations of two groups of premature infants at 6 months' corrected age. The difference in neurological development at 6 months' corrected age was statistically significant when comparison was corrected for premature infants who had neonatal seizures and periventricular hemorrhage.

Cerebrovascular disease in pediatric patients.

Although rare in childhood, stroke may have a serious impact when it happens in this stage of life. Also, it may be the first sign of a systemic disease. We report 12 cases of patients with stroke treated in the Neuropediatrics Unit of Hospital de Clínicas de Porto Alegre (HCPA) from March 1997 to March 2000. All patients, from term infants to 12-year-old children hospitalized in the Pediatrics Unit of HCPA, had clinical suspicion of stroke, which was later confirmed by radiological studies. Patient follow up ranged from 1 to 6 years (mean = 3.4 years). Presenting symptoms were hemiparesis in 9 patients, seizures in 7, deviation of labial commissure in 3, and loss of consciousness in 1. The increase in the number of cases of childhood stroke identified and later confirmed by noninvasive methods had helped in the determination of different ethiologies of stroke: the most frequent being hematologic, cardiac and genetic diseases. However, our study included 6 newborns with stroke whose ethiology was not identified. Seven children with seizures received phenobarbital. Six term infants had neonatal seizures secondary to stroke and restricted to the first 72 hours of life.

[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.

Improvement of autism spectrum disorder symptoms in three children by using gastrin-releasing peptide / Melhoria nos sistemas do transtorno do espectro autista em três crianças, utilizando peptídeo liberador de gastrina

Abstract 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 160 pmol/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.

Resumo Objetivo: Avaliar a segurança, a tolerabilidade e os possíveis efeitos terapêuticos do peptídeo liberador de gastrina em três crianças com transtorno do espectro autista. Métodos: Estudo de casuística com administração intravenosa de peptídeo liberador de gastrina na dose de 160 pmol/kg por quatro dias consecutivos. Para avaliar os resultados, foram usadas a impressão dos pais, a Escala de Classificação de Autismo na Infância (CARS) e a Escala de Impressão Clínica Global (CGI). Cada criança foi submetida a novo ciclo de peptídeo após duas semanas. As crianças foram acompanhadas por quatro semanas após o término das infusões. Resultados: O peptídeo liberador de gastrina foi bem tolerado e nenhuma criança apresentou efeitos adversos. Duas crianças apresentaram melhoria na interação social, com melhoria na atenção compartilhada e nas iniciativas de interação. Duas mostraram redução dos estereótipos e melhoria na linguagem verbal. Uma criança perdeu sua compulsão por banhos, efeito que durou duas semanas após cada ciclo de infusão. A redução média no escore da CARS foi de 2,8 pontos. Quanto à CGI, os resultados foram "minimamente melhor em duas crianças" e "muito melhor" em uma. Conclusões: Este estudo sugere que o peptídeo liberador de gastrina é seguro e pode ser efetivo na melhoria dos principais sintomas do transtorno do espectro autista, porém seus resultados devem ser interpretados com cautela. Ensaios clínicos controlados, randomizados, duplo-cegos e com maior número de crianças são necessários para melhor avaliar os possíveis efeitos terapêuticos do peptídeo liberador de gastrina sobre o autismo.

Pediatric neurotoxocariasis with concomitant cerebral, cerebellar, and peripheral nervous system involvement: case report and review of the literature.

OBJECTIVE: To alert pediatricians to the neurologic consequences of toxocariasis and to describe the first pediatric case of neurotoxocariasis with concomitant cerebral, cerebellar and peripheral nervous system involvement. DESCRIPTION: We report a case of neurotoxocariasis in a previously healthy 5-year-old boy with unusual symptoms and multi-site involvement of both the central and peripheral nervous system. Differential diagnoses are discussed and the relevant literature is reviewed. Since the early 1950s, fewer than fifty cases have been described, mostly in adult patients. COMMENTS: Although human toxocariasis is one of the most common zoonotic helminth infections, neurotoxocariasis is a rare condition, especially in pediatric patients. Although toxocariasis usually presents as a self-limiting disease with no central nervous system involvement, when it does occur, it can be devastating. Neurotoxocariasis should be added to the differential diagnosis of pediatric patients with unusual neurologic symptoms accompanied by high levels of eosinophils in the cerebrospinal fluid. Early diagnosis and treatment can prevent long-term neurologic sequelae.

[Neurologic vigor of term newborns according to the type of delivery and obstetric maneuvers]. / Vigor neurológico de recém-nascidos a termo segundo tipo de parto e realização de manobras obstétricas.

PURPOSE: to evaluate the effect of delivery type and usual obstetric procedures on the neurologic condition of a sample of consecutive term and healthy neonates, in the first 48 hours of life, using the Neurologic Adaptative Capacity Score (NACS) system. METHODS: cohort prospective study with 313 neonates, from a neonatology unit: Unidade de Neonatologia e Alojamento Conjunto. The variables analyzed were obstetric variables; clinical outcome: low neurologic vigor phase, evaluated by NACS, at 4, 24 and 48 hours of life. The data have been assessed twice: once with the whole sample and the other comparing the Vigorous Group, whose neonates kept a score of 35 or more during the three evaluations, and the Low Vigor Group, with less than 35 scores during the three consecutive evaluations. Bivariate and multivariate analyses have been done. Possible associations between low neurologic vigor phase and the type of delivery, as well between the low neurologic vigor phase and obstetric variables have been searched. RESULTS: in the bivariate analysis, the delivery type and the obstetric variables were not associated with the low neurologic vigor phase. Nevertheless, the association between the amniotic fluid and the low neurologic vigor phase reached values very close to significance and, then, it was included in the multivariate analysis. In the multivariate analysis, the only variable associated with low neurologic vigor was the presence of meconium stained amniotic fluid, which has shown to be 8.1 times more risky for the neurologic scoring, when Vigorous Group and Low Vigor Group were compared. In the analysis of the whole sample, the same risk was 1.7. CONCLUSIONS: neither the delivery type, nor the usual obstetric procedures were associated with low neurologic vigor phase. This is useful information, clinically or legally speaking, mainly for obstetricians. According to this sample data, when the term neonate is healthy, the delivery type and the usual obstetric procedures have no impact in the neurologic condition.

Neurotoxocaríase infantil com acometimento cerebral, cerebelar, e periférico simultâneo: relato de caso e revisão da literatura / Pediatric neurotoxocariasis with concomitant cerebral, cerebellar, and peripheral nervous system involvement: case report and review of the literature

OBJETIVO: Alertar a comunidade pediátrica às consequências neurológicas da toxocaríase e descrever o primeiro caso pediátrico de neurotoxocaríase com acometimento simultâneo do cérebro, cerebelo e sistema nervoso periférico. DESCRIÇÃO: Relatamos um caso de neurotoxocaríase em criança do sexo masculino, 5 anos de idade, previamente hígido, com sintomas incomuns e acometimento multifocal dos sistemas nervosos central e periférico. Discutimos o diagnóstico diferencial e fazemos uma breve revisão da literatura. Desde o início da década de 1950, menos de 50 casos de neurotoxocaríase foram descritos, a maioria em adultos. COMENTÁRIOS: A toxocaríase é uma das helmintíases mais comuns em humanos. A neurotoxocaríase, porém, é uma patologia rara, especialmente na população pediátrica. Embora a toxocaríase costume seguir um curso autolimitado, sem envolvimento do sistema nervoso central, as manifestações neurológicas podem ser devastadoras quando ocorrem. A neurotoxocaríase deve fazer parte do diagnóstico diferencial de pacientes pediátricos com sintomas neurológicos atípicos e eosinofilia no líquor. Se diagnosticada e tratada precocemente, é possível evitar as sequelas neurológicas a longo prazo.

OBJECTIVES: To alert pediatricians to the neurologic consequences of toxocariasis and to describe the first pediatric case of neurotoxocariasis with concomitant cerebral, cerebellar and peripheral nervous system involvement. DESCRIPTIONS: We report a case of neurotoxocariasis in a previously healthy 5-year-old boy with unusual symptoms and multi-site involvement of both the central and peripheral nervous system. Differential diagnoses are discussed and the relevant literature is reviewed. Since the early 1950s, fewer than fifty cases have been described, mostly in adult patients. COMMENTS: Although human toxocariasis is one of the most common zoonotic helminth infections, neurotoxocariasis is a rare condition, especially in pediatric patients. Although toxocariasis usually presents as a self-limiting disease with no central nervous system involvement, when it does occur, it can be devastating. Neurotoxocariasis should be added to the differential diagnosis of pediatric patients with unusual neurologic symptoms accompanied by high levels of eosinophils in the cerebrospinal fluid. Early diagnosis and treatment can prevent long-term neurologic sequelae.