The Development and Content Validation of a Clinical Screening Scale to Identify Attention-Deficit Hyperactivity Disorder Cases Based on the Gender Perspective: An e-Delphi Study.

BACKGROUND: Although many studies analyse gender differences in the clinical expression of Attention-Deficit Hyperactivity Disorder (ADHD) and prevalence studies show that girls with ADHD are underdiagnosed, there are no instruments that are sensitive to the detection of girls with ADHD. OBJECTIVE: The objective of this study is to develop a self-report early detection instrument for boys and girls with ADHD aged 7 to 16, which includes the gender perspective and is sensitive to the detection of girls with ADHD. METHODS: The scale was developed and the items that comprised it were created from the thematic analysis of ADHD and its evaluation in children based on the diagnostic criteria of the DSM-5-TR. A modified e-Delphi method involving a three-round web survey was used to establish a consensus on the content of the scale. Ten experts were recruited to form a professional panel. The panel members were asked to assess the differential symptomatology of ADHD in boys and girls, the dimensions to be evaluated, and the importance of scale items to evaluate the content. RESULTS: A consensus was reached regarding 13 total items distributed in three dimensions: inattention; hyperactivity/impulsivity; and, a third dimension, internalisation, which includes symptoms most present in the expression of ADHD in girls. CONCLUSIONS: To the best of our knowledge, the development of this scale using the Delphi method is the first specific scale used for identifying ADHD that also addresses the gender perspective and the differential symptomatology between boys and girls. However, we must proceed to the analysis of psychometric properties, as the scale requires an exhaustive study of its reliability and validity. We can anticipate that this scale will provide relevant and reliable information that can be used for the identification of ADHD in both boys and girls.

Glial overexpression of Tspo extends lifespan and protects against frataxin deficiency in Drosophila.

The translocator protein TSPO is an evolutionary conserved mitochondrial protein overexpressed in various contexts of neurodegeneration. Friedreich Ataxia (FA) is a neurodegenerative disease due to GAA expansions in the FXN gene leading to decreased expression of frataxin, a mitochondrial protein involved in the biosynthesis of iron-sulfur clusters. We previously reported that Tspo was overexpressed in a Drosophila model of this disease generated by CRISPR/Cas9 insertion of approximately 200 GAA in the intron of fh, the fly frataxin gene. Here, we describe a new Drosophila model of FA with 42 GAA repeats, called fh-GAAs. The smaller expansion size allowed to obtain adults exhibiting hallmarks of the FA disease, including short lifespan, locomotory defects and hypersensitivity to oxidative stress. The reduced lifespan was fully rescued by ubiquitous expression of human FXN, confirming that both frataxins share conserved functions. We observed that Tspo was overexpressed in heads and decreased in intestines of these fh-GAAs flies. Then, we further overexpressed Tspo specifically in glial cells and observed improved survival. Finally, we investigated the effects of Tspo overexpression in healthy flies. Increased longevity was conferred by glial-specific overexpression, with opposite effects in neurons. Overall, this study highlights protective effects of glial TSPO in Drosophila both in a neurodegenerative and a healthy context.

Some things old, new and borrowed: Delivery of dabrafenib and vemurafenib to melanoma cells via self-assembled nanomicelles based on an amphiphilic dendrimer.

Two clinically approved anticancer drugs targeting BRAF in melanoma patients - dabrafenib (DAB) and vemurafenib (VEM) - have been successfully encapsulated into nanomicelles formed upon self-assembly of an amphiphilic dendrimer AD based on two C18 aliphatic chains and a G2 PAMAM head. The process resulted in the formation of well-defined (∼10 nm) core-shell nanomicelles (NMs) with excellent encapsulation efficiency (∼70% for DAB and ∼60% for VEM) and good drug loading capacity (∼27% and ∼24% for DAB and VEM, respectively). Dynamic light scattering (DLS), transmission electron microscopy (TEM), small-angle x-ray scattering (SAXS), nuclear magnetic resonance (NMR), isothermal titration calorimetry (ITC), and molecular simulation (MS) experiments were used, respectively, to determine the size and structure of the empty and drug-loaded nanomicelles (DLNMs), along with the interactions between the NMs and their cargoes. The in vitro release data revealed profiles governed by Fickian diffusion; moreover, for both anticancer molecules, an acidic environment (pH = 5.0) facilitated drug release with respect to physiological pH conditions (pH = 7.4). Finally, both DAB- and VEM-loaded NMs elicited enhanced response with respect to free drug treatments in 4 different melanoma cell lines.

Drosophila CRISPR/Cas9 mutants as tools to analyse cardiac filamin function and pathogenicity of human FLNC variants.

Filamins are large proteins with actin-binding properties. Mutations in FLNC, one of the three filamin genes in humans, have recently been implicated in dominant cardiomyopathies, but the underlying mechanisms are not well understood. Here, we aimed to use Drosophila melanogaster as a new in vivo model to study these diseases. First, we show that adult-specific cardiac RNAi-induced depletion of Drosophila Filamin (dFil) induced cardiac dilatation, impaired systolic function and sarcomeric alterations, highlighting its requirement for cardiac function and maintenance of sarcomere integrity in the adult stage. Next, we introduced in the cheerio gene, using CRISPR/Cas9 gene editing, three missense variants, previously identified in patients with hypertrophic cardiomyopathy. Flies carrying these variants did not exhibit cardiac defects or increased propensity to form filamin aggregates, arguing against their pathogenicity. Finally, we show that deletions of the C-term part of dFil carrying the last four Ig-like domains are dispensable for cardiac function. Collectively, these results highlight the relevance of this model to explore the cardiac function of filamins and increase our understanding of physio-pathological mechanisms involved in FLNC-related cardiomyopathies. This article has an associated First Person interview with the first author of the paper.

Prevención de cáncer de piel en el Hospital de Clínicas: ¿qué sabe el personal de salud? / Prevention of skin cancer in the Hospital de Clínicas: what do health personnel know? / Prevenção do câncer de pele no Hospital de Clínicas: o que sabem os profissionais de saúde?

El cáncer de piel es la neoplasia maligna más frecuente en Uruguay así como a nivel mundial, donde muere una persona cada menos de cuatro días por ésta causa. La medida de prevención primaria más efectiva es tener hábitos de fotoprotección, lo cual se consigue mediante la educación en salud y campañas preventivas. En el presente trabajo se resumen los resultados del examen físico realizado a funcionarios del Hospital de Clínicas en el contexto de la Campaña de Prevención de Cáncer de Piel 2017 y los hábitos y conocimientos de fotoprotección de los mismos. La amplia mayoría de los asistentes considera que cuenta con información suficiente sobre cómo protegerse del sol, que proviene, en un 39% de los casos de la televisión. Aún asi, el 41% de ellos, sólo se protege en ocasiones especiales como viajes y verano y únicamente 3 de los participantes emplea medidas adecuadas. Con respecto a campañas previas, 94% no recordaba otra campaña de prevención de cáncer de piel y era la primera vez que concurría a una el 99% de los individuos, lo que pone en manifiesto la necesidad de reforzar la planificación y ejecución de campañas y medidas efectivas para la promoción y prevención del cáncer de piel en los próximos años a fin de lograr disminuir la incidencia de cáncer de piel que continúa en aumento.

O câncer de pele é a neoplasia maligna mais frequente no Uruguai e no mundo, onde uma pessoa morre a cada menos de quatro dias por essa causa. A medida de prevenção primária mais eficaz é ter hábitos fotoprotetores, o que é alcançado por meio de educação em saúde e campanhas preventivas. Este artigo sintetiza os resultados do exame físico realizado em funcionários do Hospital de Clínicas no contexto da Campanha de Prevenção do Câncer de Pele 2017 e seus hábitos e conhecimentos sobre fotoproteção. A grande maioria das pessoas considera que possui informações suficientes sobre como se proteger do sol, o que ocorre em 39% dos casos de televisão. Ainda assim, 41% deles são protegidos apenas em ocasiões especiais, como viagens e verão, e apenas 3 dos participantes usam medidas adequadas. Com relação às campanhas anteriores, 94% não se lembraram de outra campanha de prevenção do câncer de pele e foi a primeira vez que 99% dos indivíduos compareceram, o que evidencia a necessidade de reforçar o planejamento e a execução de campanhas e medidas eficazes para a promoção e prevenção do câncer de pele nos próximos anos, a fim de reduzir a incidência de câncer de pele que continua a aumentar.

Skin cancer is the most frequent malignancy in Uruguay as well as worldwide, where a person dies every less than four days for this cause. The most effective prevention measure is to have photoprotective habits, which is achieved through health education and preventive campaigns. This paper summarizes the results of the physical examination performed on officials of the Hospital de Clínicas in the context of the 2017 Skin Cancer Prevention Campaign and their habits and knowledge of photoprotection. The vast majority of individuals consider that they have enough information on how to protect themselves from the sun, which comes in 39% of television cases. Still, 41% of them are only protected on special occasions such as trips and summer and only 3 of the participants use adequate measures. With respect to previous campaigns, 94% did not remember another skin cancer prevention campaign and it was the first time that 99% of the individuals attended, which highlights the need to reinforce the planning and execution of campaigns and effective measures for the promotion and prevention of skin cancer in the coming years in order to reduce the incidence of skin cancer that continues to increase.

Binding of the B-Raf Inhibitors Dabrafenib and Vemurafenib to Human Serum Albumin: A Biophysical and Molecular Simulation Study.

Drug binding to human serum albumin (HSA) significantly affects in vivo drug transport and biological activity. To gain insight into the binding mechanism of the two B-Raf tyrosine kinase inhibitors dabrafenib and vemurafenib to HSA, in this work, we adopted a combined strategy based on fluorescence spectroscopy, isothermal titration calorimetry (ITC), circular dichroism (CD), and molecular simulations. Both anticancer drugs are found to bind spontaneously and with a 1:1 stoichiometry within the same binding pocket, located in Sudlow's site II (subdomain IIIA) of the protein with comparable affinity and without substantially perturbing the protein secondary structure. However, the nature of each drug-protein interactions is distinct: whereas the formation of the dabrafenib/HSA complex is more entropically driven, the formation of the alternative vemurafenib/HSA assembly is prevalently enthalpic in nature. Kinetic analysis also indicates that the association rate is similar for the two drugs, whereas the residence time of vemurafenib within the HSA binding pocket is somewhat higher than that determined for the alternative B-Raf inhibitor.

The fellowship of the RING: BRCA1, its partner BARD1 and their liaison in DNA repair and cancer.

The breast cancer type 1 susceptibility protein (BRCA1) and its partner - the BRCA1-associated RING domain protein 1 (BARD1) - are key players in a plethora of fundamental biological functions including, among others, DNA repair, replication fork protection, cell cycle progression, telomere maintenance, chromatin remodeling, apoptosis and tumor suppression. However, mutations in their encoding genes transform them into dangerous threats, and substantially increase the risk of developing cancer and other malignancies during the lifetime of the affected individuals. Understanding how BRCA1 and BARD1 perform their biological activities therefore not only provides a powerful mean to prevent such fatal occurrences but can also pave the way to the development of new targeted therapeutics. Thus, through this review work we aim at presenting the major efforts focused on the functional characterization and structural insights of BRCA1 and BARD1, per se and in combination with all their principal mediators and regulators, and on the multifaceted roles these proteins play in the maintenance of human genome integrity.

A Drosophila model of Friedreich ataxia with CRISPR/Cas9 insertion of GAA repeats in the frataxin gene reveals in vivo protection by N-acetyl cysteine.

Friedreich ataxia (FA) is caused by GAA repeat expansions in the first intron of FXN, the gene encoding frataxin, which results in decreased gene expression. Thanks to the high degree of frataxin conservation, the Drosophila melanogaster fruitfly appears as an adequate animal model to study this disease and to evaluate therapeutic interventions. Here, we generated a Drosophila model of FA with CRISPR/Cas9 insertion of approximately 200 GAA in the intron of the fly frataxin gene fh. These flies exhibit a developmental delay and lethality associated with decreased frataxin expression. We were able to bypass preadult lethality using genetic tools to overexpress frataxin only during the developmental period. These frataxin-deficient adults are short-lived and present strong locomotor defects. RNA-Seq analysis identified deregulation of genes involved in amino-acid metabolism and transcriptomic signatures of oxidative stress. In particular, we observed a progressive increase of Tspo expression, fully rescued by adult frataxin expression. Thus, Tspo expression constitutes a molecular marker of the disease progression in our fly model and might be of interest in other animal models or in patients. Finally, in a candidate drug screening, we observed that N-acetyl cysteine improved the survival, locomotor function, resistance to oxidative stress and aconitase activity of frataxin-deficient flies. Therefore, our model provides the opportunity to elucidate in vivo, the protective mechanisms of this molecule of therapeutic potential. This study also highlights the strength of the CRISPR/Cas9 technology to introduce human mutations in endogenous orthologous genes, leading to Drosophila models of human diseases with improved physiological relevance.

Executive function and general intellectual functioning in dyskinetic cerebral palsy: Comparison with spastic cerebral palsy and typically developing controls.

AIM: To comprehensively describe intellectual and executive functioning (EF) in people with dyskinetic cerebral palsy (DCP), by comparing their performance with that of: 1) age- and sex-matched typically developing controls (TDC); and 2) participants with spastic cerebral palsy (SCP) matched for age, sex, term/preterm and gross motor function classification system (GMFCS). METHOD: This cross-sectional study was conducted by the University of Barcelona in collaboration with five institutions. Participants were people with DCP (n = 52; 24 females, median age 20.5 y: 5mo, interquartile range [IQR] = 13.75 y: 7mo; GMFCS I-V). As comparison groups, participants with SCP (n = 20; 10 females, median age = 20.5 y: 5.5mo, IQR = 13.75 y 9mo; GMFCS I-V) and TDC (n = 52; 24 females, median age = 20 y: 4mo, IQR = 12 y 7mo) were included. Intelligence and EF were assessed using common tests in all participants. RESULTS: Both CP groups had lower intelligence than TDC and performed poorer in almost all EF tasks. Intelligence was higher in DCP than SCP (z = -2.51, p = 0.01). Participants with DCP also performed significantly better in goal-setting tasks (z = 2.27, p = 0.03) and information processing (z = -2.54, p = 0.01) than those with SCP. CONCLUSION: People with DCP present lower general intellectual functioning and poorer EF across multiple domains than typically developing controls. People with DCP have higher general intellectual functioning and better EF than people with SCP when levels of motor severity are similar.

Identification of cardioprotective drugs by medium-scale in vivo pharmacological screening on a Drosophila cardiac model of Friedreich's ataxia.

Friedreich's ataxia (FA) is caused by reduced levels of frataxin, a highly conserved mitochondrial protein. There is currently no effective treatment for this disease, which is characterized by progressive neurodegeneration and cardiomyopathy, the latter being the most common cause of death in patients. We previously developed a Drosophila melanogaster cardiac model of FA, in which the fly frataxin is inactivated specifically in the heart, leading to heart dilatation and impaired systolic function. Methylene Blue (MB) was highly efficient to prevent these cardiac dysfunctions. Here, we used this model to screen in vivo the Prestwick Chemical Library, comprising 1280 compounds. Eleven drugs significantly reduced the cardiac dilatation, some of which may possibly lead to therapeutic applications in the future. The one with the strongest protective effects was paclitaxel, a microtubule-stabilizing drug. In parallel, we characterized the histological defects induced by frataxin deficiency in cardiomyocytes and observed strong sarcomere alterations with loss of striation of actin fibers, along with full disruption of the microtubule network. Paclitaxel and MB both improved these structural defects. Therefore, we propose that frataxin inactivation induces cardiac dysfunction through impaired sarcomere assembly or renewal due to microtubule destabilization, without excluding additional mechanisms. This study is the first drug screening of this extent performed in vivo on a Drosophila model of cardiac disease. Thus, it also brings the proof of concept that cardiac functional imaging in adult Drosophila flies is usable for medium-scale in vivo pharmacological screening, with potent identification of cardioprotective drugs in various contexts of cardiac diseases.

Experiencia en la utilización de lisdexanfetamina en el manejo del TDAH de niños y adolescentes / Experience in the use of lisdexamfetamine in the management of ADHD of children and adolescents

INTRODUCCIÓN: El trastorno por déficit atencional e hiperactividad (TDAH) constituye uno de los trastornos más frecuentes del neurodesarrollo, con una prevalencia estimada a nivel mundial de aproximadamente el 5% [1,2]. Hasta hace pocos años, las opciones farmacológicas utilizadas en España para el tratamiento del TDAH estaban circunscritas básicamente al metilfenidato en sus diferentes presentaciones (MFD), y a la Atomoxetina (ATX). Desde el año 2014 disponemos en nuestro arsenal terapéutico del dimesilato de lisdexanfetamina (LDX); que es el primer psicoestimulante de larga duración con tecnología de profármaco, aprobado para su uso en España en niños en los que ha habido una inadecuada respuesta al tratamiento con metilfenidato, a partir de los 6 años de vida. Con el advenimiento de la Guanfancina en 2016, hemos asistido a una ampliación considerable del abanico de opciones terapéuticas farmacológicas disponibles a nuestro alcance, posibilitando de esta manera un control más efectivo de los síntomas nucleares del TDAH. OBJETIVOS: El principal objetivo de este trabajo se centra en la descripción y caracterización de una población de niños y adolescentes con diagnóstico de TDAH, en los que se realizó ensayo terapéutico con LDX. En base a los resultados obtenidos y a la revisión de la bibliografía, se presentan los diferentes "escenarios" en los cuales el uso de LDX ha demostrado ser de especial utilidad en el manejo de niños y adolescentes con TDAH. Material y MÉTODOS: Se llevó a cabo un estudio longitudinal y descriptivo, en el cual se revisaron por un lado las diferentes respuestas obtenidas con LDX en función de las características clínicas de la población objeto de análisis (niños y adolescentes de entre 6 y 18 años con diagnóstico de TDAH, previamente expuestos a diferentes pautas de MFD y/o ATX), así como el perfil de tolerabilidad y de efectos secundarios presentados. RESULTADOS: Se incluyeron en el trabajo 200 pacientes (n=200), de los cuales 140 fueron varones y 60 niñas (relación varón/niñas 2.3), con un rango de edades comprendido entre los 6 y los 18 años, y una media de edad de 15 años. De los 200 pacientes incluidos, 178 (89%) presentaron una respuesta buena o muy buena, mientras que los 22 restantes (11%) tuvieron una inadecuada respuesta y/o una tasa de efectos secundarios que motivaron la suspensión del tratamiento con LDX. Los que mejor respondieron al cambio a LDX fueron aquellos individuos en los que existía una respuesta previa parcial a diferentes pautas farmacológicas, en los que necesitaban múltiples tomas de MFD para obtener una mejor cobertura a lo largo del día, o en los que existían efectos indeseables sobre el "carácter" (especialmente en adolescentes sin otras comorbilidades asociadas). El 89% de los pacientes presentaron efectos secundarios de intensidad leve-moderada (en la línea de los ya descriptos con los psicoestimulantes), con tendencia a mejorar o desaparecer con el paso del tiempo. No se evidenciaron efectos secundarios graves en la serie analizada. CONCLUSIONES: Existe un perfil clínico de pacientes con diagnóstico de TDAH en los cuales el uso de LDX parece mostrar un alto perfil de eficacia, con una adecuada tolerabilidad a corto, mediano y largo plazo; y una aceptable tasa de efectos secundarios

INTRODUCTION: Attention deficit hyperactivity disorder (ADHD) is one of the most frequent neurodevelopmental disorders, with an estimated worldwide prevalence of approximately 5% [1,2]. Until a few years ago, the pharmacological options in Spain for the treatment of ADHD were basically confined to methylphenidate in its different presentations (MFD), and to Atomoxetine (ATX). Since 2014 we have in our therapeutic arsenal the lisdexanfetamine dimesylate (LDX); which is the first long-term psychostimulant with prodrug technology, approved for use in Spain in children in whom there has been an inadequate response to treatment with methylphenidate, from 6 years of age. With the advent of guanfancine in 2016, we have witnessed a considerable expansion of the range of pharmacological therapeutic options available to us, thus enabling a more effective control of the core symptoms of ADHD. OBJECTIVES: The main objective of this work focuses on the description and characterization of a population of children and adolescents diagnosed with ADHD, in which a LDX therapeutic trial was conducted. Based on the results obtained and the review of the literature, the different "scenarios" are presented in which the use of LDX has proved to be especially useful in the management of children and adolescents with ADHD. MATERIAL AND METHODS: A longitudinal and descriptive study was carried out, in which the different responses obtained with LDX were reviewed on the one hand according to the clinical characteristics of the population under analysis (children and adolescents between 6 and 18 years old). with a diagnosis of ADHD, previously exposed to different MFD and / or ATX guidelines), as well as the tolerability profile and side effects presented. RESULTS: 200 patients were included in the study (n = 200), of which 140 were males and 60 girls (relation between males / girls 2.3), with a range of ages between 6 and 18 years, and an average of age of 15 years. Of the 200 patients included, 178 (89%) had a good or very good response, while the remaining 22 (11%) had an inadequate response and / or a rate of side effects that led to the suspension of treatment with LDX. Those who responded best to the change to LDX were those individuals in whom there was a partial prior response to different pharmacological guidelines, in which they needed multiple doses of MFD to obtain better coverage throughout the day, or in which there were undesirable effects. about "character" (especially in adolescents without other associated comorbidities). 89% of the patients presented side effects of mildmoderate intensity (in line with those already described with psychostimulants), with a tendency to improve or disappear with the passage of time. There were no serious side effects in the series analyzed. CONCLUSIONS: There is a clinical profile of patients diagnosed with ADHD in whom the use of LDX seems to show a high efficacy profile, with adequate tolerability in the short, medium and long term; and an acceptable rate of side effects

Measuring intellectual ability in cerebral palsy: The comparison of three tests and their neuroimaging correlates.

Standard intelligence scales require both verbal and manipulative responses, making it difficult to use in cerebral palsy and leading to underestimate their actual performance. This study aims to compare three intelligence tests suitable for the heterogeneity of cerebral palsy in order to identify which one(s) could be more appropriate to use. Forty-four subjects with bilateral dyskinetic cerebral palsy (26 male, mean age 23 years) conducted the Raven's Coloured Progressive Matrices (RCPM), the Peabody Picture Vocabulary Test-3rd (PPVT-III) and the Wechsler Nonverbal Scale of Ability (WNV). Furthermore, a comprehensive neuropsychological battery and magnetic resonance imaging were assessed. The results show that PPVT-III gives limited information on cognitive performance and brain correlates, getting lower intelligence quotient scores. The WNV provides similar outcomes as RCPM, but cases with severe motor impairment were unable to perform it. Finally, the RCPM gives more comprehensive information on cognitive performance, comprising not only visual but also verbal functions. It is also sensitive to the structural state of the brain, being related to basal ganglia, thalamus and white matter areas such as superior longitudinal fasciculus. So, the RCPM may be considered a standardized easy-to-administer tool with great potential in both clinical and research fields of bilateral cerebral palsy.

Effects of internal rigid fixation on mandibular development in growing rabbits with mandibular fractures.

PURPOSE: The aim of this research was to determine whether rigid internal fixation interferes with mandibular growth and development in growing New Zealand white rabbits with induced mandibular fractures. MATERIALS AND METHODS: Ten 3-month-old New Zealand white rabbits were included in the study. Surgical fractures were performed in the right mandibular bodies of the 10 rabbits. These fractures were reduced with internal rigid fixation by use of a 1.0-mm titanium system, taking the contralateral left mandibular bodies as the control group. We obtained radiographs preoperatively and at 1, 2, and 3 months postoperatively. Predetermined cephalometric points were used to measure and compare jaw growth. The protocol was approved by the Bioethics Committee of Universidad El Bosque, Bogotá, Colombia. RESULTS: There were no statistically significant differences between the experimental and control groups (P = .95). Mandibular growth in the studied rabbits was not affected by the use of internal rigid fixation. CONCLUSIONS: The use of internal rigid fixation for the treatment of induced mandibular fractures in growing rabbits did not alter the normal process of growth and development. The findings of this study should lead to investigations using larger samples and to long-term prospective follow-up studies of children who have undergone open reduction and internal rigid fixation.

[Dissections of craniocervical arteries in the paediatric age: a pathology that is emerging or under-diagnosed?]. / Disecciones arteriales craneocervicales en la edad pediátrica: una patología emergente o infradiagnosticada?

INTRODUCTION: Cranio-cervical arterial dissections are a recognized cause of ischemic stroke in childhood, with an approximate incidence of 0.4 to 20%. AIM. To describe a population of children with cranio-cervical arterial dissections, analyzing clinical presentation, risk factors, angiographic findings, evolution and treatment. PATIENTS AND METHODS: A descriptive, retrospective, longitudinal collaborative review (Sant Joan de Deu and Pereira Rossell Children's Hospital), of children one month to 17 years old of age was conducted, during the period of time between 2000 to 2009. RESULTS: Ten cases with arterial dissection were identified, 7 of them were boys and 3 girls. Nine had a traumatism preceding neurological symptoms. Clinical presentation included 5 patients with hemiparesis, 3 with hemicerebelus syndrome, 1 with VI cranial nerve palsy and 1 with intracranial soplus as the only symptom at physical examination. Three of them had seizures, while headache preceding the onset of cerebral ischemic symptoms was founded in 6 of them. Dissection involved anterior circulation in 5 patients and posterior circulation in the other 5. In reference to the localization of arterial compromise 4 patients had intracranial dissections and 6 had extracranial dissections. Anticoagulation therapy was done in 5, antiagregation in 3, and treatment abstention in two. None of them suffered neither complications due to anticoagulation therapy nor dead or recurrent dissections in long term follow up (2 months to 8 years). CONCLUSIONS: Cranio-cervical dissections are a frequent cause of stroke in childhood. Clinical suspicious related to cranio-cervical traumatisms and subsequent neurological symptoms should be high.

Disecciones arteriales craneocervicales en la edad pediátrica: ¿una patología emergente o infradiagnosticada? / Dissections of craniocervical arteries in the paediatric age: a pathology that is emerging or under-diagnosed?

Introducción. Las disecciones craneocervicales constituyen una reconocida causa de ictus en la infancia y adolescencia, y son responsables del 0,4-20% del total de casos. Objetivo. Describir una población de niños con disecciones arteriales, analizando su presentación clínica, factores de riesgo, signos angiográficos, evolución y tratamiento. Pacientes y métodos. Se llevó a cabo un estudio descriptivo, retrospectivo y colaborativo (Hospital Sant Joan de Déu de Barcelona y Centro Hospitalario Pereira Rossell de Montevideo), durante los años 2000 a 2009, de niños entre 1 mes a 17 años, con disecciones arteriales craneocervicales. Resultados. Se identificaron 10 casos con diagnóstico de disección arterial, siete varones y tres niñas. Nueve presentaron traumatismo previo al inicio de los síntomas neurológicos. Del total de pacientes, cinco comenzaron con hemiparesia, tres con síndrome hemicerebeloso, uno con afectación del VI par, y uno con soplo craneal. De éstos, tres tuvieron convulsiones y seis cefaleas que precedieron al cuadro clínico. El deterioro de la circulación anterior tuvo lugar en cinco niños, y l de la posterior en los otros cinco. Cuatro pacientes presentaron afectación arterial intracraneal, y seis, extracraneal. Se realizó anticoagulación en cinco pacientes, antiagregación en tres y no se trataron los dos restantes. No hubo fallecimientos, complicaciones por la anticoagulación, ni recurrencias en el período de seguimiento clínico. Conclusiones. Las disecciones craneocervicales son una causa frecuente de ictus en la infancia. La sospecha clínica debe ser alta ante todo paciente con sintomatología focal neurológica en relación con un traumatismo craneocervical (AU)

Introduction. Cranio-cervical arterial dissections are a recognized cause of ischemic stroke in childhood, with an approximate incidence of 0.4 to 20%. Aim. To describe a population of children with cranio-cervical arterial dissections, analyzing clinical presentation, risk factors, angiographic findings, evolution and treatment. Patients and methods. A descriptive, retrospective, longitudinal collaborative review (Sant Joan de Déu and Pereira Rossell Children’s Hospital), of children one month to 17 years old of age was conducted, during the period of time between 2000 to 2009. Results. Ten cases with arterial dissection were identified, 7 of them were boys and 3 girls. Nine had a traumatism preceding neurological symptoms. Clinical presentation included 5 patients with hemiparesis, 3 with hemicerebelus syndrome, 1 with VI cranial nerve palsy and 1 with intracranial soplus as the only symptom at physical examination. Three of them had seizures, while headache preceding the onset of cerebral ischemic symptoms was founded in 6 of them. Dissection involved anterior circulation in 5 patients and posterior circulation in the other 5. In reference to the localization of arterial compromise 4 patients had intracranial dissections and 6 had extracranial dissections. Anticoagulation therapy was done in 5, antiagregation in 3, and treatment abstention in two. None of them suffered neither complications due to anticoagulation therapy nor dead or recurrent dissections in long term follow up (2 months to 8 years). Conclusions. Cranio-cervical dissections are a frequent cause of stroke in childhood. Clinical suspicious related to craniocervical traumatisms and subsequent neurological symptoms should be high (AU)

Acquired neuromyotonia in childhood: case report and review.

Recently characterized as an immune-mediated channelopaty, Isaacs' syndrome (also known as acquired neuromyotonia) was first described in 1961 in two men with persistent, generalized muscle stiffness, in addition to spontaneous, rapid discharges of motor-unit potentials on electromyography. In the peripheral nervous system, antibodies targeted to voltage-gated potassium channels induce hyperexcitability of motor axons, resulting in signs of muscle stiffness or of pseudomyotonia. A spontaneous burst of single motor-unit activity, and myokymic and neuromyotonic discharges, are the most characteristic features found in electromyography studies. This report describes Isaacs' syndrome in a child, in whom the diagnosis was made by clinical features of acquired, spontaneous muscle overactivity and typical electromyographic findings.

Bilateral segmental neurofibromatosis: a case report and review.

Bilateral segmental neurofibromatosis is a rare condition characterized by the occurrence of neurofibromas and/or café-au-lait spots limited to an area or segment of the body bilaterally. It is caused by a postzygotic mutation in the neurofibromatosis type I gene, resulting in a phenotype of genetic mosaicism. This report describes a case of bilateral segmental neurofibromatosis with multiple nodules sitting on a café-au-lait spot.

Hemoptisis en la infancia: Un desafío diagnóstico-terapéutico para el pediatra: A propósito de dos casos clínicos / Hemoptysis in childhood: A diagnosis and therapeutic challenge to the pediatrician: About two clinical cases

Se presentan los casos clínicos de dos niños previamente sanos con hemoptisis sin repercusión hemodinámica, en quienes se arribó al diagnóstico de malformación arteriovenosa mediante arteriografía. Se realizó tratamiento médico mediante embolización del lecho vascular patológico, siendo favorable la evolución clínica, con resolución de la enfermedad subyacente y alta temprana a domicilio, sin complicaciones. La arteriografía permitió realizar un diagnóstico temprano, así como la prevención de nuevas complicaciones.

Two cases of previously healthy children who suffered hemoptysis without hemodynamic compromise are presented. An underlying arteriovenous malformation by arteriography was identified in both cases. Endovascular treatment was performed using selective bronchial artery embolectomy of the anomalous vessels with an excellent recovery of both patients with no further complications. Arteriography played a vital role in early diagnosis and treatment avoiding new complications.

Déficit de succínico semialdehído deshidrogenasa: Primer caso de aciduria 4 OH butírica en Uruguay

Resumen El déficit de succínico semialdehído deshidrogenasa es una enfermedad rara cuya alteración en la vía catabólica del ácido aminobutírico (principal neurotransmisor del sistema nervioso central) impide el paso de ácido succínico semialdehído a ácido succínico, condicionando un aumento de ácido 4 hidroxibutírico en líquido cefalorraquídeo y plasma, lo que permite la detección de la enfermedad. La clínica es muy inespecífica, pudiendo presentar desde retraso psicomotor, hipotonía, convulsiones y ataxia no progresiva, hasta trastornos de conducta con crisis de ansiedad y rasgos autistas. Los hallazgos a nivel electroencefalográfico incluyen enlentecimiento del ritmo de base, con descargas epileptiformes focales o generalizadas. En la neuroimagen, en tanto, pueden hallarse frecuentemente hiperintensidades bilaterales y simétricas en T2, a nivel del núcleo pálido. Si bien el tratamiento con vigabatrina teóricamente inhibe la formación de succínico semialdehído con la consecuente reducción de los niveles de ácido 4 hidroxibutírico, no existe al momento actual un tratamiento efectivo para todos los casos. El principal objetivo de este artículo es presentar un paciente con deficiencia de succínico semialdehído deshidrogenasa, debido a su excepcionalidad, con solamente 350 casos identificados en el mundo, siendo el primer caso diagnosticado en Uruguay.

Summary Succinic semialdehyde dehydrogenase deficiency is a rare disorder of the catabolic pathway of gamma-aminobutyric acid, the major central nervous system inhibitory neurotransmitter. Because of such deficiency, transamination of gamma-aminobutyric acid to succinic semialdehyde is shunted towards the production of 4-hydroxybutyric acid, a neurotoxic metabolite which becomes abundant in physiologic fluids which allows the detection of the disorder. Clinical features are not specific and consist of psychomotor retardation, seizures, hypotonia and non progressive ataxia. Electroencephalographic finding include background slowing and generalized or focal epileptiform discharges. Magnetic resonance imaging reveals in most of the cases, increased T2-weighted signal of the globus pallidi bilaterally and symmetrically. Eventhough vigabatrin should theoretically inhibit the formation of succinic semialdehyde and therefore 4-hydroxybutyric acid, to date there is no effective treatment for succinic semialdehyde dehydrogenase deficiency. Due to its uniqueness, the main objective of this article is to present a patient with succinic semialdehyde dehydrogenase deficiency, with only 350 cases identified worldwide.

Succinic semialdehyde dehydrogenase (SSADH) deficiency: Molecular analysis in a South American family.

We report the clinical, biochemical and molecular findings on the first documented patient with 4-hydroxybutyric aciduria (4-HBA, McKusick 271980) from Uruguay. The patient displayed a severe picture and turned out to be homozygous for a mutation (c.1226G < A) previously shown to be associated with null enzyme activity.