Ethical Dimensions in Paediatric Neurology: A Look into the Future

Les professionnels de la santé et les familles pour qui des enfants qui participent à la recherche en génétique ou qui nécessitent des services génétiques spécialisés, y compris, le dépistage génétique, seront confrontés à des interrogations non seulement médicales, mais sociales, éthiques et juridiques liées à la génétique en neurologie pédiatrique. Les enfants se retrouvent souvent au centre d’innovations dans le cadre de recherches en génétique et leurs besoins uniques soulèvent des inquiétudes quant aux risques et aux bénéfices associés à cette recherche. Plus précisément, le consentement, l’utilisation de base de données génétique et la thérapie génique soulèvent des enjeux particuliers. En plus de ces enjeux, des risques psychologiques peuvent aussi leur être associés. À la lumière de l’analyse de lignes directrices nationales et internationales, il sera question, dans cet article, des bénéfices et de l’impact des technologies génétiques chez l’enfant. Les médecins, les législateurs et les familles doivent être informés de ces lignes directrices et doivent comprendre les enjeux éthiques et psychologiques liés à la génétique en neurologie pédiatrique. // Health care providers and families with children who participate in genetic research or who need specialized genetic services, including genetic testing, will encounter not only medical but difficult social, ethical, and legal questions surrounding pediatric genetic neurology. Children are often at the center of much of the genetic revolution and their unique needs raise special concerns about the risks and the benefits associated with genetic research, particularly the issues of consent, the use of genetic databases, and gene therapy. Moreover, genetic research and testing raise important psychosocial risks. In this article we discuss some of the benefits and consequences of genetic technologies for children in relation to national and international guidelines. In particular, physicians, policy-makers, and families should be knowledgeable about the guidelines and have good understanding of the psychosocial and ethical issues associated with genetics in pediatric neurology.

Prevalence of Epilepsy in Children From a Brazilian Area of High Deprivation

This study assessed the prevalence rate of epilepsy and its causes in children and adolescents in one area of high deprivation in Sao Paulo, Sao Paulo, in Southeast Brazil. Between July 2005 and June 2006, 4947 families from a population of 22,013 inhabitants (including 10,405 children and adolescents between the ages of 0 and 16 years) living in the shantytown of Paraisopolis, were interviewed. In the first phase, a validated questionnaire was administered, to identify the occurrence of seizures. In the second phase, clinical history, neurologic examination, electroencephalography, and structural neuroimaging were performed. The diagnosis of epilepsy, including etiology, seizure types, and epileptic syndrome classification, was according to criteria of the International League Against Epilepsy. The screening phase identified 353 presumptive cases. In the second phase, 101 of these cases (33.8%) received the diagnosis of epilepsy. Crude prevalence of epilepsy was 9.7/1000 and prevalence of active epilepsy was 8.7/1000. Partial seizures were the most frequent seizure type (62/101). Symptomatic focal epilepsy was the most common form, and hypoxic-ischemic encephalopathy the most common etiology, reflecting the socioeconomic conditions of this specific population. Adequate public policies regarding perinatal assistance could help reduce the prevalence of epilepsy. (C) 2010 by Elsevier Inc. All rights reserved.

Primary Disorders of Neurotransmitter Metabolism: Experience of a Tertiary Center

Neurotransmitter diseases are a group of inherited disorders attributable to a disturbance of neurotransmitter metabolism. Biogenic amines are neurotransmitters with multiple roles including psychomotor function, hormone secretion, cardiovascular, respiratory and gastrointestinal control, sleep mechanisms, body temperature and pain. Given the multiple functions of monoamines, disorders of their metabolism comprise a wide spectrum of manifestations, with motor dysfunction being the most prominent clinical feature. Methods: Case review of 12 patients from 4 families, with primary disorders of biogenic amine metabolism. Results: Aromatic L-amino acid decarboxylase deficiency (4 patients from 2 families), and GTP-cyclohydrolase (8 patients from 2 families) were the two diseases identified. Age at first symptoms varied between 2 months and 6 years. Developmental delay was present in all cases except 2 patients with GTP cyclohydrolase deficiency. The combination of axial hypotonia and limb dystonia was also frequent. Children with aromatic L-amino acid decarboxylase deficiency exhibited temperature instability, oculogyric crisis and disturbances of sleep. The index case of one family with GTP cyclohydrolase deficiency presented with Parkinsonism (bradykinesia, rigidity and hypomimia). Analysis of neurotransmitters and their metabolites in CSF was crucial for the identification of index cases. Response to therapy was variable but in general unsatisfactory except in a family with GTP cyclohydrolase deficiency. Conclusions: These disorders should be considered in the differential diagnosis of paediatric neurodegenerative diseases, in order to allow an adequate therapeutic trial that can favor prognosis.

GM1 Gangliosidosis, Late Infantile Onset Dystonia, and T2 Hypointensity in the Globus Pallidus and Substantia Nigra

BACKGROUND: GM1 gangliosidosis is a rare disease due to mutations in the GLB1 gene and autosomal recessive deficiency of b-galactosidase. There is considerable overlap between classical phenotypes and clinical and imaging findings, which are often difficult to interpret. PATIENT: The patient in this study had dysmorphism, dysostosis, progressive dystonia, and T2 hypointensity in the basal ganglia. Partially similar clinical and radiologic findings were described previously in two reports. CONCLUSIONS: T2 hypointensity in the globus pallidus should, in the appropriate clinical setting, lead to consideration of thediagnosis of GM1 gangliosidosis.

MRI following severe perinatal asphyxia: preliminary experience.

In 30 children suffering from severe perinatal asphyxia an attempt was made to determine the early prognostic signs of severe hypoxic-ischemic brain injury with magnetic resonance imaging (MRI). Ten early (1-4 days of age), 16 intermediate (2-4 weeks of age), and 38 late MRI (older than 1 month of age) procedures were performed on a 2.35 T MR-system. Severe cerebral necrosis was suspected by T2 hyperintensity of the white matter, with blurred limits to the cortex in early MRI, and was confirmed by T1 hyperintensity of the cortex in intermediate MRI. Severe cerebral necrosis was established at 3 months of age. Of the 11 children with this pattern (group A), 8 had severe and 3 had moderate cerebral palsy on subsequent examination. Thirteen children (group B) had normal late MRI scans; none developed severe cerebral palsy or marked mental retardation. Two children (group C) had focal ischemic lesions. Four children had intracranial hemorrhage (group D). Groups A and B did not differ in the severity of their perinatal histories and findings, suggesting that MRI during the first 3 months is of significant prognostic value.

When is a child with status epilepticus likely to have Dravet syndrome?

PURPOSE: To identify clinical risk factors for Dravet syndrome (DS) in a population of children with status epilepticus (SE). MATERIAL AND METHODS: Children aged between 1 month and 16 years with at least one episode of SE were referred from 6 pediatric neurology centers in Switzerland. SE was defined as a clinical seizure lasting for more than 30min without recovery of normal consciousness. The diagnosis of DS was considered likely in previously healthy patients with seizures of multiple types starting before 1 year and developmental delay on follow-up. The presence of a SCN1A mutation was considered confirmatory for the diagnosis. Data such as gender, age at SE, SE clinical presentation and recurrence, additional seizure types and epilepsy diagnosis were collected. SCN1A analyses were performed in all patients, initially with High Resolution Melting Curve Analysis (HRMCA) and then by direct sequencing on selected samples with an abnormal HRMCA. Clinical and genetic findings were compared between children with DS and those with another diagnosis, and statistical methods were applied for significance analysis. RESULTS: 71 children with SE were included. Ten children had DS, and 61 had another diagnosis. SCN1A mutations were found in 12 of the 71 patients (16.9%; ten with DS, and two with seizures in a Generalized Epilepsy with Febrile Seizures+(GEFS+) context). The median age at first SE was 8 months in patients with DS, and 41 months in those with another epilepsy syndrome (p<0.001). Nine of the 10 DS patients had their initial SE before 18 months. Among the 26 patients aged 18 months or less at initial SE, the risk of DS was significantly increased for patients with two or more episodes (56.3%), as compared with those who had only one episode (0.0%) (p=0.005). CONCLUSION: In a population of children with SE, patients most likely to have DS are those who present their initial SE episode before 18 months, and who present with recurrent SE episodes.

El autismo en el primer año

Actualmente es posible diagnosticar el autismo con un alto grado de fiabilidad entre los 18 meses y los 2 años. Sin embargo, los primeros síntomas ya están presentes mucho antes del diagnóstico. Ello ha dado pie a que se hayan llevado a cabo múltiples estudios, retrospectivos y prospectivos, orientados a detectar manifestaciones que faciliten un diagnóstico lo más precozmente posible. A partir de estas investigaciones se han podido detectar síntomas cuya aparición se sitúa entre los 6 y 12 meses. Aunque se ha visto que estos síntomas tienen un interés diagnóstico limitado, aportan información muy valiosa para la comprensión del autismo en el marco de los trastornos del neurodesarrollo, en el sentido de destacar un patrón evolutivo que en su inicio es común a diversos trastornos, pero que progresivamente va configurando un fenotipo específico.

Electrical status epilepticus during sleep. Continuous spikes and waves during sleep

ABSTRACT Maria Peltola Electrical status epilepticus during sleep – Continuous spikes and waves during sleep Department of Clinical Neurophysiology, University of Turku Department of Clinical Neurophysiology and Department of Pediatric Neurology, Children’s Hospital, Helsinki University Central Hospital Annales Universitatis Turkuensis, Medica-Odontologica, Turku, Finland, 2014 Background: Electrical status epilepticus during sleep (ESES) is an EEG phenomenon of frequent spikes and waves occurring in slow sleep. ESES relates to cognitive deterioration in heterogeneous childhood epilepsies. Validated methods to quantitate ESES are missing. The clinical syndrome, called epileptic encephalopathy with continuous spikes and waves during sleep (CSWS) is pharmacoresistant in half of the patients. Limited data exists on surgical treatment of CSWS. Aims and methods: The effects of surgical treatment were studied by investigating electroclinical outcomes in 13 operated patients (nine callosotomies, four resections) with pharmacoresistant CSWS and cognitive decline. Secondly, an objective paradigm was searched for assessing ESES by the semiautomatic quantification of spike index (SI) and measuring spike strength from EEG. Results: Postoperatively, cognitive deterioration was stopped in 12 (92%) patients. Three out of four patients became seizure-free after resective surgery. Callosotomy resulted in greater than 90% reduction of atypical absences in six out of eight patients. The preoperative propagation of ESES from one hemisphere to the other was associated with a good response. Semiautomatic quantification of SI was a robust method when the maximal interspike interval of three seconds was used to determine the “continuous” discharge in ten EEGs. SI of the first hour of sleep appeared representative of the whole night SI. Furthermore, the spikes’ root mean square was found to be a stable measure of spike strength when spatially integrated over multiple electrodes during steady NREM sleep. Conclusions: Patients with pharmacoresistant CSWS, based on structural etiology, may benefit from resective surgery or corpus callosotomy regarding both seizure outcome and cognitive prognosis. The semiautomated SI quantification, with proper userdefined settings and the new spatially integrated measure of spike strength, are robust and promising tools for quantifying ESES. Keywords: Electrical status epilepticus during sleep, ESES, continuous spikes and waves during sleep, CSWS, epilepsy surgery, spike index, spike strength, RMS TIIVISTELMÄ Maria Peltola Unenaikainen sähköinen status epilepticus Kliininen neurofysiologia, Turun yliopisto Kliininen neurofysiologia ja lastenneurologia, Lasten ja nuorten sairaala, Helsingin yliopistollinen keskussairaala Annales Universitatis Turkuensis, Medica-Odontologica, Turku, Suomi, 2014 Tausta: Sähköinen status epilepticus unessa (ESES) on aivosähkökäyrä (EEG)-ilmiö, jossa hidasaaltounen aikana esiintyy tiheä piikkihidasaaltopurkaus. ESES:n kvantifioimiseen ei ole olemassa validoituja menetelmiä. ESES on liitetty kognitiivisen tason laskuun ja tällöin puhutaan CSWS (continuous spikes and waves during sleep) - oireyhtymästä. CSWS ei vastaa lääkehoitoon puolella potilaista ja sen epilepsiakirurgisesta hoidosta on olemassa vain vähän tietoa. Tavoitteet ja menetelmät: Selvitimme retrospektiivisesti epilepsiakirurgian vaikusta elektrokliinisiin löydöksiin 13:lla lääkeresistenttiä CSWS-oireyhtymää sairastavalla lapsella, joilla oli rakenteellinen aivojen poikkeavuus. Toinen tavoite oli löytää objektiivinen puoliautomaattinen tapa mitata purkauksen määrää ja piikkien voimakkuutta EEG:stä. Tulokset: Kognitiivisen tason jatkuva heikentyminen loppui 12 (92 %) potilaalla leikkauksen jälkeen. Kolme neljästä resektiopotilaasta tuli kohtauksettomaksi. Kallosotomian jälkeen kuudella kahdeksasta potilaasta päivittäiset kohtaukset vähenivät yli 90 %:lla. Purkauksen leviäminen leikkausta edeltävästi vain yhdestä hemisfääristä toiseen liittyi hyvään leikkaushoitovasteeseen. Piikki-indeksi, jossa käytetään jatkuvan purkauksen määritelmänä maksimissaan kolmea sekuntia piikkien välillä, osoittautui luotettavaksi menetelmäksi ESES:n kvantifioimiseen. Useammasta elektrodista integroitu piikkien neliöllinen keskiarvo oli piikin voimakkuuden vakaa mitta häiriintymättömässä NREM-unessa. Päätelmät: Lääkehoidolle vastaamatonta CSWS:ää sairastavat potilaat, joilla on rakenteellinen aivopoikkeavuus ja yhdensuuntainen purkauksen leviämismalli, näyttävät kohtausten vähenemisen lisäksi hyötyvän epilepsiakirurgiasta kognitiivisesti. Puoliautomaattinen piikki-indeksin kvantifiointi sopivilla käyttäjäasetuksilla ja uusi spatiaalisesti integroitu piikin voimakkuuden mittari ovat stabiileja ja lupaavia ESES:n kvantitatiivisia mittareita. Avainsanat: Unenaikainen sähköinen status epilepticus, ESES, CSWS, epilepsiakirurgia, piikki-indeksi, piikin voimakkuus, neliöllinen keskiarvo

Prevalencia de TSH neonatal elevada y factores perinatales relacionados con asfixia Bogotá 2012

Introducción: la asfixia perinatal es la tercera causa de muerte en menores de 5 años. Las secuelas neurológicas suponen una carga importante para las familias y los sistemas de salud (1). Los estudios que relacionan el efecto de la asfixia perinatal sobre las hormonas tiroideas son escasos. El estudio sobre predictores de asfixia es un tema de investigación permanente. El objetivo principal fue determinar la prevalencia de TSH de cordón elevada y su relación con factores perinatales asociados a asfixia. Métodos: estudio descriptivo retrospectivo. La muestra estuvo conformada por todos los recién nacidos con TSH de cordón elevada y un segundo grupo seleccionado de forma aleatoria con TSH de cordón normal. Tomada de una población de neonatos atendidos en una clínica de Bogotá durante el 2012. Resultados: la prevalencia de TSH de cordón elevada fue de 14,7%. Los resultados sugieren una posible asociación entre alteraciones en las pruebas de bienestar fetal, presencia de infección materna, parto distócico, dificultad respiratoria y APGAR bajo y la presencia de TSH elevada p<0,05. Discusión: La alta prevalencia de TSH de cordón elevada podría relacionarse con las características de alto riesgo que presenta esta población. La elevación transitoria de la TSH neonatal de cordón en neonatos con alteraciones del bienestar fetal asociada a eventos hipóxicos agudos, sugiere que esta hormona podría ser un marcador de asfixia perinatal.

Equinoterapia en niños con autismo

Introducción: Autismo es un trastorno del desarrollo caracterizado por compromiso en interacción social, habilidades de lenguaje, presentando rituales con estereotipias. Sin tratamientos curativos, actualmente se buscan terapias alternativas. Un incremento de la literatura científica de terapias asistidas con animales se ha evidenciado, demostrando mejoría en pacientes autistas con la equinoterapia. Objetivo: Realizar una revisión sistemática de la literatura para evaluar efectividad de la equinoterapia en habilidades sociales y de lenguaje en niños autistas. Metodología: Revisión sistemática de la literatura de artículos obtenidos en bases de datos y Meta-buscadores que proporcionaron evidencia de equinoterapia en niños autistas. Tipo de artículos consultados: revisiones sistemáticas, meta análisis y ensayos clínicos. Trabajos publicados hasta 2013. En inglés y español. Se emplearon términos MeSH y EMTREE. Resultados: Cuatro artículos cumplieron criterios de inclusión y exclusión. Se analizaron los artículos individualmente, no se logró realizar un meta análisis por diferencias metodológicas entre los estudios. En total 85 sujetos fueron evaluados en dichos estudios. La equinoterapia en niños autistas evidenció mejoría en habilidades sociales y en las habilidades de lenguaje pre verbal. Discusión: La equinoterapia es prometedora en el manejo de niños autistas, los artículos evidencian consistentemente mejorías a nivel de habilidades sociales y de lenguaje. Debe ser considerado el tipo de paciente, el régimen de equinoterapia y la sostenibilidad de las mejoras. Conclusiones: Se necesitan nuevos estudio con un mayor rigor metodológico que permitan fortalecer la evidencia sobre la equinoterapia en niños con autismo y así poder realizar recomendaciones con un adecuado nivel de evidencia.

Experience With Lacosamide in a Series of Children With Drug-Resistant Focal Epilepsy

We report our pediatric experience with lacosarnide, a new antiepileptic drug, approved by the US Food and Drug Administration as adjunctive therapy in focal epilepsy in patients more than 17 years old. We retrospectively reviewed charts for lacosamide use and seizure frequency outcome in patients with focal epilepsy (Wilcoxon signed rank test). Sixteen patients (7 boys) were identified (median dose 275 mg daily, 4.7 mg/kg daily; mean age 14.9 years, range 8-21 years). Patients were receiving a median of 2 antiepileptic drugs (interquartile range [IQR] 1.7-3) in addition to having undergone previous epilepsy surgery (n = 3), vagus nerve stimulation (n = 9), and ketogenic diet (n = 3). Causes included structural (encephalomalacia and diffuse encephalitis, 1 each; stroke in 2) and genetic abnormalities (Aarskog and Rett syndromes, 1 each) or cause not known (n = 10). Median seizure frequency at baseline was 57 per month (IQR 7-75), and after a median follow-up of 4 months (range 1-13 months) of receiving lacosamide, it was 12.5 per month (IQR 3-75), (P < 0.01). Six patients (37.5%; 3 seizure free) were classified as having disease that responded to therapy (>= 50% reduction seizure frequency) and 10 as having disease that did not respond to therapy (<50% in 3; increase in 1; unchanged in 6). Adverse events (tics, behavioral disturbance, seizure worsening, and depression with suicidal ideation in 1 patient each) prompted lacosamide discontinuation in 4/16 (25%). This retrospective study of 16 children with drug-resistant focal epilepsy demonstrated good response to adjunctive lacosamide therapy (median seizure reduction of 39.6%; 37.5% with >= 50% seizure reduction) without severe adverse events. (C) 2011 Elsevier Inc. All rights reserved.

Unusual Presentation of Brain Aspergillosis in Chronic Granulomatous Disease

Aspergillus is a frequently observed pathogen in patients with chronic granulomatous disease. We report on a patient with chronic granulomatous disease and severe brain aspergillosis with an unusual presentation and favorable course. We discuss the impact of this infection on morbidity and mortality, adequate therapeutic management, and the need to investigate a possible fungal infection, despite nonspecific signs. (C) 2010 by Elsevier Inc. All rights reserved.

A prática de atividade física de crianças e adolescentes com e sem epilepsia

The epilepsy is one of the neurological disorders more common in the pediatric period, and which interferes significantly in the psycho and social life of children and teenagers. The objective of this study was analyzing the practice of sedentary practices, physicals, traditional infant fun and games of children and teenagers with and without epilepsy. The study was prospective, transversal descriptive, done with 60 children and teenagers with epilepsy (Epileptic Group - EG) patients from Pediatric Neurology Clinic of the Centre Integrated Health Lineu Araújo and 60 children and teenagers without epilepsy (Control Group - CG) students from municipal public school, both of the two groups paired with the same age (age group 7 to 14 years) of both the genders (female = 25/41,6% and male = 35/58,3%) of the Teresina city Piauí. It was done two pattern questionnaires, one applied to children and teenagers of the EG and CG to identify the sedentary activities, physical and traditional infant games and other to the parents/responsible of the EG about the clinical and demographic information. The results permitted the elaboration of two manuscripts: a) the first one titled The Practice of Sedentary and Physical Activities of Children and Teenagers with Epilepsy which showed significant difference in the sedentary activities of playing with car toy (p=0,021) to the EG and reading to the CG (p=0,001); in the physical activities the school physical education (p=0,001) and riding a bike (p=0,014) to the CG; b) the second one The Practice of Infant Games and Fun the children and teenagers with and without Epilepsy in this one the playing with marble presented significant difference (p=0,016) to the CG, despite the girls of the two groups don t do this activity. Observing the distribution of frequencies, it was verified that in the play catch-up and hide-and-seek and burn the EG plays more than the CG both in female and male gender. The girls of the EG play less skip, 60 while the boys of the two groups don t play. Elastic jump the girls of the two groups play in a same frequency and the boys don t participate of this fun. The seizures were found to occur during: soccer (23,3%); hide-and-seek (6,6%) and running (3,3%). In the sedentary activities, seizures were reported to occur: resting and watching TV (18,3%), sleeping (36,0%); sitting (13,3%) and lying down (11,7%). Our results showed that the epileptic group and the controls group engage in the same activities, although the epileptic group participates less than the controls. Although the EG had presented a bigger percentage of generalized attacks, they don t occur during the practice of formal physical activities. The research was developed by a multidisciplinary team, and this contributed a lot to the realization of this study

Hiperglicemia no perioperatório de pacientes pediátricos submetidos à ressecção de tumores do sistema nervoso central: incidência e prognóstico

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

A avaliação do pensamento lógico em pacientes com TDAH - Transtorno de Déficit de Atenção com ou sem hiperatividade

Pós-graduação em Pediatria - FMB