[Autism. Genetic and biological aspects]. / Autismo. Aspectos genéticos y biológicos.

Autism is a neurodevelopmental disorder characterized by commitment to social interaction and communication, associated with interests restricted and stereotyped behaviors with a high population prevalence, neurobiological bases and high heritability. Its etiology is heterogeneous, numerous genetic bases, environmental factors and epigenetic mechanisms have been recognized. Advances in molecular genetics, as well as epidemiological studies of large cohorts, have made it possible to identify specific medical entities, as well as genes and environmental factors partially or totally linked in their pathogenesis. This knowledge, according to the clinical characteristics, allows to guide the complementary studies, the therapeutic conducts, to infer a clinical prognosis and to propitiate the familiar genetic advice. In this work, the most prevalent clinical characteristics identified are described; the specific medical entities that are strongly related to autism are stated, as well as the recognized genes, the possible environmental factors and the epidemiological results that allow family counseling.

El autismo es un trastorno del neurodesarrollo caracterizado por compromiso en la interacción social y la comunicación, asociado a intereses restringidos y conductas estereotipadas con gran prevalencia poblacional, bases neurobiológicas y alta heredabilidad. Su etiología es heterogénea y se han reconocido numerosas bases genéticas, factores ambientales y mecanismos epigenéticos. Los avances en la genética molecular, así como los estudios epidemiológicos de grandes cohortes, han posibilitado identificar entidades médicas específicas, así como genes y factores ambientales vinculados parcial o totalmente en su patogenia. Estos conocimientos, conforme las características clínicas, permiten orientar los estudios complementarios, las conductas terapéuticas, inferir un pronóstico clínico y propiciar el asesoramiento genético familiar. En este trabajo analizamos las características clínicas de los trastornos del espectro del autismo, las entidades médicas específicas que están fuertemente relacionadas a los mismos, así como los genes reconocidos, los posibles factores ambientales y los resultados epidemiológicos que permiten el adecuado asesoramiento familiar.

[Aging in people with autism spectrum disorder].

Autism spectrum disorder is characterized by a qualitative alteration in social interaction and communication associated with restricted interests and stereotyped behaviors. This condition will accompany people throughout their lives, with variations in their evolution. Our objectives were to know the evolutionary characteristics of people with autistic spectrum disorder, analyzing cognitive, behavioral, health, mortality and their needs in the aging stage, which will guide the planning of specific support resources. We analyze studies related to the evolution in adult life in people with this disorder, with or without identified entities, and socio-health conditions that should be considered in the aging process. The knowledge about aging in people with autism is still scarce and it is difficult to define a specific pattern because this will depend, among other factors, on the etiology, the degree, the presence of intellectual disability and/or epilepsy, and the scope in where live, which can even condition the life expectancy. Aging has been associated with mood disorders, depression, deterioration in executive functions and episodic memory, although it is difficult to differentiate it from natural aging in people with typical development. The identification of a specific entity will allow to know the possible evolution and prevent complications in syndromes that may be associated with autism: fragile X, Down, Angelman, Rett and Williams, for that reason we rank the genetic and neurological consultation.

[Autism and camouflage]. / Autismo y camuflaje.

Autism is a neurobiologically based neurodevelopmental disorder with high prevalence and a clear predominance in males. It is characterized by deficits in social cognition and communication, restricted interests, and stereotyped behaviors, frequently associated with sensory dysfunction others neurodevelopmental conditions, neuropsychiatric disorders, epilepsy, and/or sleep disorders. This condition will accompany people throughout their lives, which will generate various support and treatment needs. People with autism often need to "fit in" and for this they use techniques such as camouflage, also called masking. This attitude has been observed in people with typical development and in people with autism in childhood, adolescence and adult life, although in autistic people this behavior is more intense and takes longer and with more frequency and intensity in autistic adult women. This could explain the underreporting of autism, the later diagnosis, the delay in the therapeutic approach, and the greater presence of anxiety and depression disorders related to the effort that "appearing normal" implies. Even though camouflage people appear to be "normal" and fit in perfectly, this is not an attitude that we should promote and, on the contrary, it is imperativeto work to improve the environment and the understanding of each person. In this paper we will analyze the clinical aspects, their relationship with age, sex, and ways of detecting it.

El autismo es un trastorno del neurodesarrollo de base neurobiológica con alta prevalencia y claro predomino en varones. Se caracteriza por déficits en la cognición social y la comunicación, intereses restringidos y conductas estereotipadas, frecuentemente asociado a disfunciones sensoriales, otras condiciones del neurodesarrollo, trastornos neuropsiquiátricos, epilepsia y/o trastornos de sueño. Esta condición acompañará a las personas a lo largo de toda la vida, lo cual generará diversas necesidades de apoyo y tratamientos. Las personas con autismo muchas veces necesitan "encajar", para ello utilizan técnicas como el camuflaje, también denominada enmascaramiento. Esta actitud se ha observado en personas con desarrollo típico y en personas con autismo en la infancia, adolescencia y vida adulta, aunque en los autistas esta conducta es más intensa y lleva más tiempo, y se la identifica con más frecuencia e intensidad en mujeres adultas autistas. Esto podría explicar el subregistro de autismo, el diagnóstico más tardío, el retraso en el abordaje terapéutico y la mayor presencia de trastornos de ansiedad y depresión relacionados al esfuerzo que implica "parecer normal". Si bien las personas al camuflar parecen ser "normales" y encajan perfectamente, ésta no es una actitud que debiera propiciarse, por el contrario es imperativo trabajar para mejorar el entorno y la comprensión de cada persona. En este trabajo analizamos los aspectos clínicos, su relación con la edad, sexo, y formas de detección del mismo.

[Autism and epigenetics. A model of explanation for the understanding of the genesis in autism spectrum disorders]. / Autismo y epigenética. Un modelo de explicación para la comprensión de la génesis en los trastornos del espectro autista.

Autism spectrum disorders are characterized by impairment of social integration and language development and restricted interests. Autism spectrum disorders manifest during childhood and may have a varying clinical expression over the years related to different therapeutic approaches, behavior-modifying drugs, and environmental factors, among others. So far, the genetic alterations identified are not sufficient to explain the genesis of all these processes, as many of the mutations found are also present in unaffected individuals. Findings on the underlying biological and pathophysiological mechanisms of entities strongly associated with autism spectrum disorders, such as Rett, fragile X, Angelman, and fetal alcohol syndromes, point to the role of epigenetic changes in disorders of neurodevelopment. Epigenetic phenomena are normal biological processes necessary for cell and thus human life, especially related to embryonic development. Different phenomena that affect epigenetic processes (changes that change operation or expression of a gene, without modifying the DNA structure) have also been shown to be important in the genesis of neurodevelopmental disorders. Alterations in the epigenetic mechanism may be reversible, which may explain the variation in the autism phenotype over time. Here we analyze the normal epigenetic mechanisms, autism spectrum disorders, their association with specific entities associated with altered epigenetic mechanisms, and possible therapeutic approaches targeting these alterations.

[Acute encephalitis anti-ionotropic glutamate receptor activated N-methyl-D-aspartate (NMDAR): analysis of eleven pediatric cases in Argentina (Benito Yelín Award)]. / Encefalitis aguda mediada por anticuerpos contra el receptor ionotrópico de glutamato activado por N-metil-D-aspartato (NMDAR): análisis de once casos pediátricos en Argentina (Premio Benito Yelín).

Encephalitis are an inflammatory processes of various origin, among which include autoimmune origin. The identification of antibodies against the N-methyl-D- aspartate, allowed clinical immunological characterization of an entity susceptible to immunomodulatory therapy. Originally described in young women associated with ovarian teratoma, is now a recognized entity in children even in the absence of detectable tumors. The aim of the study was conducted through review of medical records, was to describe the clinical, developmental and findings in further studies of eleven children with confirmed diagnosis of this entity through identification of specific antibodies. All debuted with psychiatric symptoms in nine associating seizures, and two extrapyramidal movements. In the evolution of language all had commitment nine severe autonomic symptoms, one with hypoventilation and requirements of ARM. Brain MRI was abnormal in three. Eight had voltage EEG asymmetry and / or amplitude, three of them had spikes. Six had CSF pleocytosis and three of seven positive oligoclonal bands. Five IgM serology for mycoplasma were positive. CPK increase occurred in conjunction with antisychotics in five. With immunomodulatory treatment, five had complete recovery three behavioral disorders / cognitive deficits and one severe. A patient's clinical picture resolved without treatment. In any associated tumor was detected. We conclude that in front of a child with acute encephalopathy and clinical support this entity after infectious cause were ruled out, immunomodulatory therapy should be started early, avoid the use of antipsychotic drugs and search for possible hidden tumors.

[Autism. Pharmacological treatment]. / Autismo. Tratamiento farmacológico.

Autism is a neurodevelopmental disorder characterized by deficits in social cognition and communication, restricted interests, and stereotyped behaviors. Frequently associated with sensory dysfunction, other neurodevelopmental disorders, neuropsychiatric disorders, epilepsy and/or sleep disorders. This condition will accompany people throughout their lives, which will generate various support and treatment needs. Although there are no drugs that modify the core symptoms of autism, various drugs have shown their usefulness in associated conditions. Atypical antipsychotics for hyperactivity, impulsivity, agitation, auto or heteroaggression crises. Serotonin reuptake inhibitors, to decrease anxiety, obsessive-compulsive symptoms, and irritability/agitation. Stimulants and atomoxetine used for hyperactivity, inattention, and impulsivity. Clonidine and guanfacine show some efficacy on hyperactivity and stereotyped behaviors. Buspirone has been used for restrictive behaviors and anxiety. There are drugs in the research phase such as oxytocin, vasopressin and even some developed for specific entities related to autism such as arbaclofen in Fragile X and Trofinetide that has just been approved for use in Rett syndrome. As specific entities and their pathophysiology are identified, it is likely that tailored treatments will be developed for each entity associated with autism..

El autismo es un trastorno del neurodesarrollo caracterizado por déficits en la cognición social y la comunicación, intereses restringidos y conductas estereotipadas. Frecuentemente asociado a disfunciones sensoriales, otros trastornos del neurodesarrollo, trastornos neuropsiquiátricos, epilepsia y/o trastornos de sueño. Esta condición acompañará a las personas a lo largo de toda la vida, lo cual generará diversas necesidades de apoyo y tratamientos. Si bien no existen fármacos que modifiquen los síntomas nucleares del autismo diversos medicamentos han demostrado su utilidad en condiciones asociadas. Los antipsicóticos atípicos para la hiperactividad, la impulsividad, la agitación, las crisis de auto o heteroagresión. Los inhibidores de la recaptación de serotonina, para disminuir la ansiedad, los síntomas obsesivo-compulsivos y la irritabilidad/agitación. Los estimulantes y la atomoxetina utilizados para la hiperactividad, la falta de atención y la impulsividad. La clonidina y la guanfacina muestran cierta eficacia sobre la hiperactividad y las conductas estereotipadas. La buspirona se ha utilizado para los comportamientos restrictivos y la ansiedad. Existen medicamentos en fase de investigación como la oxitocina, la vasopresina e incluso algunos desarrollados para entidades específicas relacionadas con el autismo como arbaclofeno en Frágil X y la Trofinetida que acaba ser aprobada para su uso en el síndrome de Rett. En la medida que se identifiquen entidades específicas y su fisiopatología es probable que se desarrollen tratamientos a la medida para cada entidad asociada con autismo.

[Autism and catatonia - Clinical aspects]. / Autismo y catatonía - Aspectos clínicos.

Autism is a neurodevelopmental disorder characterized by a qualitative alteration in social interaction and communication, associated with restricted interests and stereotyped behaviors. It can be associated with medical problems such as epilepsy, gastrointestinal dysfunction, sleep disorders, other neurodevelopmental disorders such as language impairment, intellectual disability, sensory dysfunction, ADH/D, motor clumsiness, and/or neuropsychiatric disorders such as anxiety, depression, catatonia, schizophrenia, obsessive-compulsive disorders, behavioral and impulsive disorders, among others. Catatonia is recognized as a neuropsychiatric syndrome identified in all major mood and psychotic disorders, due to general medical conditions or as a syndrome not otherwise specified; this allows catatonia to be coded in the context of other psychiatric or neurodevelopmental disorders, such as obsessive-compulsive disorder or autism. It is characterized by abnormal motor, vocal, and behavioral symptoms, with impaired volition and vegetative function. It is estimated that approximately 8-11% of autistic people suffer from catatonia. It is probable that there is an underreporting of catatonia, especially in people with autism, due to the lack of alertness about it, the clinical heterogeneity and the similarity of many of its symptoms with manifestations of autism. Many times it can even express itself as a late autistic regression from puberty to adult life. Its neurobiological bases are still not clear and the treatment is based on the administration of bensodiazepines and electroconvulsive therapy although there is still a long way to go to investigate these issues.

El autismo es un desorden del neurodesarrollo caracterizado por una alteración cualitativa en la interacción social y la comunicación, asociada a intereses restringidos y conductas estereotipadas. Puede asociarse a problemas médicos como epilepsia, disfunciones gastrointestinales, trastornos de sueño, otros trastornos del neurodesarrollo como deterioro del lenguaje, discapacidad intelectual, disfunciones sensoriales, TDA/H, torpeza motriz y/o trastornos neuropsiquiátricos como ansiedad, depresión, catatonia, esquizofrenia, trastornos obsesivo-compulsivo, trastornos de conducta e impulsividad, entre otros.La catatonía es reconocida como un síndrome neuropsiquiátrico identificado en todos los tra stornos psicóticos y del estado de ánimo mayor, debido a condiciones médicas generales o como un síndrome no especificado de otra manera; esto permite codificar la catatonia en el contexto de otros trastornos psiquiátricos o del neurodesarrollo, como el trastorno obsesivo compulsivo o el autismo. Se caracteriza por síntomas motores, vocales y conductuales anormales, con alteración de la volición y la función vegetativa. Se estima que aproximadamente entre el 8 y 11 % de las personas autistas padecen catatonia. Es probable que haya un subregistro de catatonía, en especial en personas con autismo, debido a la falta de alerta sobre la misma, la heterogenicidad clínica y la similitud de muchos de sus síntomas con manifestaciones del autismo. Incluso muchas veces puede expresarse como una regresión autista tardía desde la pubertad a la vida adulta. Sus bases neurobiológicas aún no son claras y el tratamiento se basa en la administración de bensodiazepinas y la terapia electroconvulsiva, aunque es mucho el camino que aún queda por investigar en estos temas.

[Autism throughout life]. / El autismo a lo largo de la vida.

Autism is a neurodevelopmental disorder characterized by deficits in social cognition and communication, restricted interests, and stereotyped behaviors. It is often associated with sensory dysfunctions, other neurodevelopmental disorders, neuropsychiatric disorders, epilepsy and/or sleep disorders. This condition will accompany people throughout their lives, with variations in its evolution. In the last ten years, only 1% of all autism research focused on developing post-secondary education programs and training in adult health services. Taking into account this dichotomy of interests, we must think about the different stages of life, such as early intervention, school inclusion, bullying, associated mental and medical disorders, lack of group belonging, job opportunities and the aging. Only by becoming aware of each of them can we achieve a better quality of life for people with autism and their families.

El autismo es un trastorno del neurodesarrollo de base neurobiológica caracterizado por déficits en la cognición social y la comunicación, intereses restringidos y conductas estereotipadas. Muchas veces está asociado a disfunciones sensoriales, otros trastornos del neurodesarrollo, trastornos neuropsiquiátricos, epilepsia y/o trastornos de sueño. Esta condición acompañará a las personas a lo largo de toda la vida, con variaciones en su evolución. En los últimos diez años solo el 1% de todas las investigaciones en autismo se centraron en desarrollar programas de educación post secundaria, y formación de servicios de salud para adultos. Teniendo en cuenta esta dicotomía de intereses es que debemos pensar en las diferentes etapas de la vida, cómo el abordaje temprano, la inclusión escolar, el hostigamiento, los trastornos mentales y médicos asociados, la falta de grupo de pertenencia, las oportunidades laborales y el envejecimiento. Solamente tomando conciencia de cada una de ellas podremos lograr una mejor calidad de vida de las personas con autismo y sus familias.

[Autism. Neurobiological aspects]. / Autismo. Aspectos neurobiológicos.

Autism is a neurodevelopmental disorder with a neurobiological basis, characterized by a qualitative disturbance in social interaction and communication, associated with restricted interests and stereotyped behaviors. The genesis of autism cannot be interpreted through a single theory, and we can't compartmentalize brain areas as the only ones responsible for it. Among the neurobiological bases we can include: deficit in the social reward system, which generates poor social initiative; dysfunctions and disorders of the amygdala and the mirror neuron system, related to compromised empathy and social cognition; abnormalities in the minicolumns related to hyper-systematization; persistent inflammatory phenomena of the central nervous system related to microglia; alterations of neuropeptides such as oxytocin, vasopressin and cortisol, which compromise socialization, and neuronal inhibition disorders, expressed in GABAergic dysfunctions in interneurons, linked to autistic behaviors, epilepsy and sensory phenomena. Understanding the neurobiological bases of autism is complex and there is no single explanation or specific biological marker. However, identifying processes related to social cognition, molecular, inflammatory, neuromodulation mechanisms and bases linked to sensory disorders are fundamental elements.

El autismo es un trastorno del neurodesarrollo de base neurobiológica, caracterizado por una alteración cualitativa en la interacción social y la comunicación, asociado a intereses restringidos y conductas estereotipadas. La génesis del autismo no puede interpretarse a través de una sola teoría, tampoco podemos compartimentalizar áreas del cerebro como únicos responsables de la misma. Entre las bases neurobiológicas podemos incluir: déficit en el sistema de recompensa social, lo cual genera pobre iniciativa social; disfunciones y trastornos de la amígdala y el sistema de neuronas espejo, relacionadas al compromiso en la empatía y la cognición social; anormalidades en las minicolumnas relacionadas con la hiper-sistematización; fenómenos inflamatorios persistentes del sistema nervioso central relacionados a la microglía; alteraciones de los neuropéptidos como oxitocina, vasopresina y cortisol, que comprometen la socialización, y trastornos en la inhibición neuronal, expresados en disfunciones gabaérgicas en las inteneuronas, vinculadas a conductas autistas, epilepsia y fenómenos sensoriales. La comprensión de las bases neurobiológicas del autismo son complejas y no existe un marcador biológico específico. Sin embargo, identificar procesos relacionados a la cognición social, mecanismos moleculares, inflamatorios, de neuromodulación y bases vinculadas a trastornos sensoriales son elementos fundamentales.

[Epigenetic mechanisms involved in the genesis of autism]. / Mecanismos epigenéticos involucrados en la génesis del autismo.

Autism is a neurobiological developmental disorder characterized by poor social interaction and communication, narrow interests, and stereotyped behaviors. It has been associated with disorders of synaptogenesis and multiple etiologies. The identification of the epigenetic factors involved in the genesis of autism allows a better understanding of the molecular mechanisms involved. Our objective was to analyze the epigenetic mechanisms related to the development of autism, specifying specific entities and their pathophysiological mechanisms. We analyze how DNA methylation disorders, histone modification, remodeling and chromosomal regulation mediated by non-coding RNA are related to various genetic syndromes such as fragile X, Rett, Pathias Mecp2, Phelam McDermid, prenatal toxins such as alcohol, valproic. acid, cannabis, and environmental toxins such as maternal stress, all associated with a higher prevalence of autism. In conclusion: the recognition of these mechanisms opens up new possibilities for prevention and it is likely that, in genetic entities, it will allow the development of specific treatments with modifications tailored to each entity.

El autismo es un trastorno del neurodesarrollo de base neurobiológica, caracterizado por alteración en la interacción social y la comunicación, intereses restringidos y conductas estereotipadas. Se relaciona con trastornos en la sinaptogénesis y a multiples etiologías. La identificación de factores epigenéticos implicados en la génesis del autismo permiten una mejor comprensión de los mecanismos moleculares involucrados. Nuestro objetivo fue analizar los mecanismos epigenéticos relacionados al desarrollo del autismo, puntualizando entidades específicas y sus mecanismos fisiopatológicos. Analizamos de qué manera se relacionan los trastornos en la metilación del ADN, la modificación de las histonas, la remodelación cromosómica y la regulación mediada por el ARN no codificantes con diversos síndromes genéticos como el frágil X, Rett, Mecp2patías, Phelam McDermid, tóxicos prenatales como el alcohol, ácido valproico, cannabis y ambientales cómo el estrés materno, todos ellos asociados a una mayor prevalencia de autismo. En conclusión, el reconocimiento de estos mecanismos abre nuevas posibilidades para la prevención, y probablemente en un futuro, en las entidades genéticas, permitirá el desarrollo de tratamientos específicos con modificaciones a la medida de cada entidad.

[Autism, depression and risk of suicide]. / Autismo, depresión y riesgo de suicidio.

Autism is a neurodevelopmental disorder characterized by a qualitative alteration in social interaction and communication, associated with restricted interests and stereotyped behaviors. People with autism are four times more likely to develop depression, than the general population, it is even considered as the most common mental health condition in people with autism spectrum disorders (ASD). One of the challenges is to recognize the manifestations related to depression in people with ASD, in whom, in general, it is expressed differently in relation to those with typical development. Depression in people with autism can manifest itself with restlessness and insomnia and not with feelings of sadness, so it is essential to be attentive and not justify all behavioral problems to autism. Young adults with ASD have higher baseline levels of almost all the depression characteristics listed in the DSM-5, which can lead to overdiagnosis or underreporting of depression. On the other hand, adults with autism have an increased risk of experiencing suicidal thoughts, planning suicide, carrying it out and even dying from suicide. Many of them have a history of depression, harassment and loneliness. It is essential the early detection of depression, develop appropriate tools for diagnosis in autism as well as generate awareness of the risk of ideation or suicide, a problem that only in recent years has been addressed with greater depth. In this paper I analyze depression in autism, the risk of suicidal ideation and suicide, prioritizing clinical aspects, their evaluation and risk factors.

El autismo es un desorden del neurodesarrollo caracterizado por una alteración cualitativa en la interacción social y la comunicación, asociada a intereses restringidos y conductas estereotipadas. Las personas con autismo tienen cuatro veces más posibilidades de desarrollar depresión que la población general y es considerada la afección de salud mental más frecuente en personas con trastornos del espectro autista (TEA). Es difícil reconocer la depresión en personas con TEA, en quienes, en general, se expresa en forma diferente a las que tienen desarrollo típico. En ellos la depresión puede manifestarse con inquietud e insomnio y no con sentimientos de tristeza, como sería esperable, por ello es esencial estar atentos y no justificar todos los problemas al autismo. Los adultos jóvenes con TEA tienen niveles basales más altos de casi todas las características de depresión enumeradas en el DSM-5, esto puede generar sobrediagnóstico o subregistro de depresión. Los adultos con autismo tienen un riesgo aumentado de experimentar pensamientos suicidas, planificarlo, llevarlo a cabo e incluso fallecer por suicidio. Muchos de ellos tienen antecedentes de depresión, padecimiento de hostigamiento y sensación de soledad. Es fundamental la detección temprana de depresión, desarrollar herramientas adecuadas para su diagnóstico en autismo, y generar conciencia de riesgo de ideación o suicidio, lo que recién en los últimos años ha sido abordado con mayor profundidad. En este trabajo se analizan la depresión en autismo, el riesgo de ideación suicida y suicidio, jerarquizando los aspectos clínicos, su evaluación y factores de riesgo.

[Genetic syndromes recognizable in the neonatal period]. / Síndromes genéticos reconocibles en el período neonatal.

The presence of a neonatal neurological lesion associated or not with dysmorphism or with a particular phenotype can be caused by a) prenatal infections (Group TORCH) toxic or teratotoxic agents (alcohol, cocain, antiepileptics, inhalants such as toluene, etc.), vascular defects or genetic anomalies; b) perinatal isquemic hypoxic lesions, infectious or metabolic disorders, etc. In this paper we analyze all entities of genetic origin neonatally recognizable by their phenotype which must be included in the differential diagnosis of all children neurologically compromised. In order to simplify the diagnosis, these entities will be divided according to the prevalence of the phenotype present at birth, dividing them into two large groups: 1) Genic alterations which include: Syndromes with characteristic facies and member malformations, Supra growth syndrome, Syndrome with neonatal growth deficit, Neuro-ectodermic syndromes, Syndromes with characteristic facies and ocular compromise, Syndromes with characteristic facies including those that bear MIM number, and 2) Chromosomal alterations (autosomal in number, mosaic, deletion, and sex chromosomes). The detection of these anomalies through phenotype studies involving congenital encephalopathies of genetic origin is of major importance because it will permit the orientation of specific diagnostic studies, the prevention of difficult and expensive maneuvers, and furthermore, it will offer adequate family counseling and control eventual complications.

Autismo y camuflaje / Autism and camouflage

Resumen El autismo es un trastorno del neurodesarrollo de base neurobiológica con alta prevalencia y claro predo mino en varones. Se caracteriza por déficits en la cog nición social y la comunicación, intereses restringidos y conductas estereotipadas, frecuentemente asociado a disfunciones sensoriales, otras condiciones del neuro desarrollo, trastornos neuropsiquiátricos, epilepsia y/o trastornos de sueño. Esta condición acompañará a las personas a lo largo de toda la vida, lo cual generará diversas necesidades de apoyo y tratamientos. Las personas con autismo muchas veces necesitan "encajar", para ello utilizan técnicas como el camuflaje, también denominada enmascara miento. Esta actitud se ha observado en personas con desarrollo típico y en personas con autismo en la infan cia, adolescencia y vida adulta, aunque en los autistas esta conducta es más intensa y lleva más tiempo, y se la identifica con más frecuencia e intensidad en mujeres adultas autistas. Esto podría explicar el subregistro de autismo, el diagnóstico más tardío, el retraso en el abordaje tera péutico y la mayor presencia de trastornos de ansiedad y depresión relacionados al esfuerzo que implica "pa recer normal". Si bien las personas al camuflar parecen ser "normales" y encajan perfectamente, ésta no es una actitud que debiera propiciarse, por el contrario es imperativo trabajar para mejorar el entorno y la com prensión de cada persona. En este trabajo analizamos los aspectos clínicos, su relación con la edad, sexo, y formas de detección del mismo.

Abstract Autism is a neurobiologically based neurodevelop mental disorder with high prevalence and a clear pre dominance in males. It is characterized by deficits in social cognition and communication, restricted inter ests, and stereotyped behaviors, frequently associated with sensory dysfunction others neurodevelopmental conditions, neuropsychiatric disorders, epilepsy, and/or sleep disorders. This condition will accompany people throughout their lives, which will generate various sup port and treatment needs. People with autism often need to "fit in" and for this they use techniques such as camouflage, also called masking. This attitude has been observed in people with typical development and in people with autism in childhood, adolescence and adult life, although in autistic people this behavior is more intense and takes longer and with more frequency and intensity in autistic adult women. This could explain the underreporting of autism, the later diagnosis, the delay in the therapeutic approach, and the greater presence of anxiety and depression disorders related to the effort that "appearing normal" implies. Even though camouflage people appear to be "normal" and fit in perfectly, this is not an attitude that we should promote and, on the contrary, it is imperative to work to improve the environment and the under standing of each person. In this paper we will analyze the clinical aspects, their relationship with age, sex, and ways of detecting it.

Aging and Autism: Understanding, Intervention and Proposals to Improve Quality of Life.

BACKGROUND: The population with autism spectrum disorder (ASD) has been increasing and is currently estimated to be 1 in 58 births. The increased prevalence of ASD together with the lack of knowledge on the processes of aging in this population, the support needed at this stage of life, and the associated risk factors, have led to an urgent need for further research. METHODS: This study provides a review of the literature on social- and health-related conditions that may appear when persons with ASD grow old. RESULTS: In addition to the autism-related conditions, different neurological, genetic, and environmental factors may be involved in the process of aging. In this complex setting, this study provides proposals that may guide the development of support services that may improve the quality of life for aging people with ASD. CONCLUSION: Aging in ASD is emerging as a growing problem, which requires immediate planning and targetted treatment development.

Autismo y catatonía - Aspectos clínicos / Autism and catatonia - Clinical aspects

Resumen El autismo es un desorden del neurodesarrollo caracterizado por una alteración cualitativa en la interacción social y la comunicación, asociada a intereses restringidos y conductas estereotipadas. Puede asociarse a problemas médicos como epilepsia, disfunciones gastrointestinales, trastornos de sueño, otros trastornos del neurodesarrollo como deterioro del lenguaje, discapacidad intelectual, disfunciones sensoriales, TDA/H, torpeza motriz y/o trastornos neuropsiquiátricos como ansiedad, depresión, catatonia, esquizofrenia, trastornos obsesivo-compulsivo, trastornos de conducta e impulsividad, entre otros. La catatonía es reconocida como un síndrome neuropsiquiátrico identificado en todos los trastornos psicóticos y del estado de ánimo mayor, debido a condiciones médicas generales o como un síndrome no especificado de otra manera; esto permite codificar la catatonia en el contexto de otros trastornos psiquiátricos o del neurodesarrollo, como el trastorno obsesivo compulsivo o el autismo. Se caracteriza por síntomas motores, vocales y conductuales anormales, con alteración de la volición y la función vegetativa. Se estima que aproximadamente entre el 8 y 11 % de las personas autistas padecen catatonia. Es probable que haya un subregistro de catatonía, en especial en personas con autismo, debido a la falta de alerta sobre la misma, la heterogenicidad clínica y la similitud de muchos de sus síntomas con manifestaciones del autismo. Incluso muchas veces puede expresarse como una regresión autista tardía desde la pubertad a la vida adulta. Sus bases neurobiológicas aún no son claras y el tratamiento se basa en la administración de bensodiazepinas y la terapia electroconvulsiva, aunque es mucho el camino que aún queda por investigar en estos temas.

Abstract Autism is a neurodevelopmental disorder characterized by a qualitative alteration in social interac tion and communication, associated with restricted interests and stereotyped behaviors. It can be associated with medical problems such as epilepsy, gastrointestinal dysfunction, sleep disorders, other neurodevelopmental disorders such as language impairment, intellectual disability, sensory dysfunction, ADH/D, motor clumsiness, and/or neuropsychiatric disorders such as anxiety, depression, catatonia, schizophrenia, obsessive-compulsive disorders, behavioral and impulsive disorders, among others. Catatonia is recognized as a neuropsychiatric syn drome identified in all major mood and psychotic disorders, due to general medical conditions or as a syndrome not otherwise specified; this allows catatonia to be coded in the context of other psychiatric or neurodevelopmental disorders, such as obsessive-compulsive disorder or autism. It is characterized by abnormal motor, vocal, and behavioral symptoms, with impaired volition and vegetative function. It is estimated that approximately 8-11% of autistic people suffer from catatonia. It is probable that there is an underreporting of catatonia, especially in people with autism, due to the lack of alertness about it, the clinical heterogeneity and the similarity of many of its symptoms with manifestations of autism. Many times it can even express itself as a late autistic regression from puberty to adult life. Its neurobiological bases are still not clear and the treatment is based on the administration of bensodiazepines and electroconvulsive therapy although there is still a long way to go to investigate these issues.

Autismo. Tratamiento farmacológico / Autism. Pharmacological treatment

Resumen El autismo es un trastorno del neurodesarrollo carac terizado por déficits en la cognición social y la comu nicación, intereses restringidos y conductas estereoti padas. Frecuentemente asociado a disfunciones senso riales, otros trastornos del neurodesarrollo, trastornos neuropsiquiátricos, epilepsia y/o trastornos de sueño. Esta condición acompañará a las personas a lo largo de toda la vida, lo cual generará diversas necesidades de apoyo y tratamientos. Si bien no existen fármacos que modifiquen los sín tomas nucleares del autismo diversos medicamentos han demostrado su utilidad en condiciones asociadas. Los antipsicóticos atípicos para la hiperactividad, la impulsividad, la agitación, las crisis de auto o hete roagresión. Los inhibidores de la recaptación de serotonina, para disminuir la ansiedad, los síntomas obsesivo-compulsi vos y la irritabilidad/agitación. Los estimulantes y la atomoxetina utilizados para la hiperactividad, la falta de atención y la impulsividad. La clonidina y la guanfacina muestran cierta eficacia sobre la hiperactividad y las conductas estereotipadas. La buspirona se ha utilizado para los comportamien tos restrictivos y la ansiedad. Existen medicamentos en fase de investigación como la oxitocina, la vasopresina e incluso algunos desarrollados para entidades específicas relacionadas con el autismo como arbaclofeno en Frágil X y la Trofinetida que acaba ser aprobada para su uso en el síndrome de Rett. En la medida que se identifiquen entidades especí ficas y su fisiopatología es probable que se desarrollen tratamientos a la medida para cada entidad asociada con autismo.

Abstract Autism is a neurodevelopmental disorder charac terized by deficits in social cognition and communica tion, restricted interests, and stereotyped behaviors. Frequently associated with sensory dysfunction, other neurodevelopmental disorders, neuropsychiatric disor ders, epilepsy and/or sleep disorders. This condition will accompany people throughout their lives, which will generate various support and treatment needs. Although there are no drugs that modify the core symptoms of autism, various drugs have shown their usefulness in associated conditions. Atypical antipsychotics for hyperactivity, impulsivity, agitation, auto or heteroag gression crises. Serotonin reuptake inhibitors, to de crease anxiety, obsessive-compulsive symptoms, and irritability/agitation. Stimulants and atomoxetine used for hyperactivity, inattention, and impulsivity. Clonidine and guanfacine show some efficacy on hyperactivity and stereotyped behaviors. Buspirone has been used for restrictive behaviors and anxiety. There are drugs in the research phase such as oxytocin, vasopressin and even some developed for specific entities related to autism such as arbaclofen in Fragile X and Trofinetide that has just been approved for use in Rett syndrome. As speci fic entities and their pathophysiology are identified, it is likely that tailored treatments will be developed for each entity associated with autism.

[Pervasive developmental disorders. Clinical and genetics aspects]. / Trastornos generalizados del desarrollo. Aspectos clínicos y genéticos.

Pervasive developmental disorders (PDD) encompass a heterogeneous group of children with deficits of verbal and non-verbal language, social communication, and with a restricted repertoire of activities or repetitive behaviours. The frequency in general population is considered 27.5/10,000. In this study, we analyzed the clinical and genetic aspects of Autism, Asperger Syndrome, PDD Not Otherwise Specified, Rett Syndrome and Childhood Disintegrative Disorder. We analyzed clinical, behavioural and neuropsychological features. We revised different medical genetics associated conditions and divided the genetics aspects of pervasive developmental disorders into two groups: Syndromic forms (around 20%) and non syndromic forms (currently proposed to be 80%). The early recognition of pervasive developmental disorders and the diagnosis of specific associated syndromes allow early therapy, correct genetic counselling, and follow up anticipating possible complications related to the entity. Finally, although the genetic bases of autism have not yet been identified, the following candidate genes have been proposed: 15q, 2q, 17q, 7q, 12q, and X related genes, among others; which are analyzed in this study and will allow a better understanding of these disorders in the future.

El autismo a lo largo de la vida / Autism throughout life

Resumen El autismo es un trastorno del neurodesarrollo de base neurobiológica caracterizado por déficits en la cognición social y la comunicación, intereses restringidos y conductas estereotipadas. Muchas veces está asociado a disfunciones sensoriales, otros trastornos del neurodesarrollo, trastornos neuropsiquiá tricos, epilepsia y/o trastornos de sueño. Esta condición acompañará a las personas a lo largo de toda la vida, con variaciones en su evolución. En los últimos diez años solo el 1% de todas las investigaciones en autismo se centraron en desarrollar programas de educación post secundaria, y formación de servicios de salud para adultos. Teniendo en cuenta esta dicotomía de intereses es que debemos pensar en las diferentes etapas de la vida, cómo el abordaje temprano, la inclusión escolar, el hostigamiento, los trastornos mentales y médicos asociados, la falta de grupo de pertenencia, las oportunidades laborales y el envejecimiento. Solamente tomando conciencia de cada una de ellas podremos lograr una mejor calidad de vida de las personas con autismo y sus familias.

Abstract Autism is a neurodevelopmental disorder characterized by deficits in social cognition and communication, restricted interests, and stereotyped behaviors. It is often associated with sensory dysfunctions, other neurodevelopmental disorders, neuropsychiatric disorders, epilepsy and/or sleep disorders. This condition will accompany people throughout their lives, with variations in its evolution. In the last ten years, only 1% of all autism research focused on developing post-secondary education programs and training in adult health services. Taking into account this dichotomy of interests, we must think about the different stages of life, such as early intervention, school inclusion, bullying, associated mental and medical disorders, lack of group belonging, job opportunities and the aging. Only by becoming aware of each of them can we achieve a better quality of life for people with autism and their families.

Mecanismos epigenéticos involucrados en la génesis del autismo / Epigenetic mechanisms involved in the genesis of autism

Resumen El autismo es un trastorno del neurodesarrollo de base neurobiológica, caracterizado por alteración en la interacción social y la comunicación, intereses restringidos y conductas estereotipadas. Se relaciona con trastornos en la sinaptogénesis y a multiples etiologías. La identificación de factores epigenéticos implicados en la génesis del autismo permiten una mejor comprensión de los mecanismos moleculares invo lucrados. Nuestro objetivo fue analizar los mecanismos epigenéticos relacionados al desarrollo del autismo, puntualizando entidades específicas y sus mecanismos fisiopatológicos. Analizamos de qué manera se rela cionan los trastornos en la metilación del ADN, la modificación de las histonas, la remodelación cromosómica y la regulación mediada por el ARN no codificantes con diversos síndromes genéticos como el frágil X, Rett, Mecp2patías, Phelam McDermid, tóxicos prenatales como el alcohol, ácido valproico, cannabis y ambientales cómo el estrés materno, todos ellos asociados a una mayor prevalencia de autismo. En conclusión, el recono cimiento de estos mecanismos abre nuevas posibilidades para la prevención, y probablemente en un futuro, en las entidades genéticas, permitirá el desarrollo de tratamientos específicos con modificaciones a la medida de cada entidad.

Abstract Autism is a neurobiological developmental disorder characterized by poor social interaction and communication, narrow interests, and stereotyped behaviors. It has been associated with disorders of synaptogenesis and multiple etiologies. The iden tification of the epigenetic factors involved in the genesis of autism allows a better understanding of the molecular mechanisms involved. Our objective was to analyze the epigenetic mechanisms related to the development of autism, specifying specific entities and their pathophysiological mechanisms. We analyze how DNA methylation disorders, histone modification, remodeling and chromosomal regulation mediated by non-coding RNA are related to various genetic syndromes such as fragile X, Rett, Pathias Mecp2, Phelam McDermid, prenatal toxins such as alcohol, valproic. acid, cannabis, and environmental toxins such as maternal stress, all associated with a higher prevalence of autism. In conclusion: the recognition of these mechanisms opens up new possibilities for preven tion and it is likely that, in genetic entities, it will allow the development of specific treatments with modifications tailored to each entity.

Enterovirus D68 infection in a cluster of children with acute flaccid myelitis, Buenos Aires, Argentina, 2016.

OBJECTIVE: To report a outbreak of 11 cases of acute asymmetric flaccid myelopathy due to spinal motor neuron injury. MATERIAL AND METHODS: Eleven children, six male, with a mean age of 3 years presented with acute flaccid myelitis. We analyzed clinical features, etiology, neuroradiological images, treatment, and outcome. RESULTS: Nine children had bilateral and asymmetric flaccid myelitis of the upper limbs, 1 had upper limb monoplegia, and 1 presented with hemiparesis. The cranial nerves were involved in 6 patients and 4 required mechanical ventilation. In all cases acute flaccid myelitis co-occurred with upper airway infection and/or fever. Spinal cord magnetic resonance imaging was abnormal in all, showing 2 different patterns: A linear pattern involving the anterior horns and another that was more heterogeneous showing spinal cord expansion. The lesions were non-enhancing in all. In 5/11 patients involvement of the medulla oblongata and pons was also observed. None of the patients presented with supratentorial lesions. In 4/11 children, the human enterovirus subtype D68 (HEV-D68) was identified in the airway and in 1/11 in the cerebrospinal fluid as well. In the remaining patients different enterovirus species A, B, and C variants were detected, as well as rhinovirus in 1 and influenza in another. Ten children received treatment with intravenous immunoglobulin and steroids and 4 of these children also underwent plasma exchange. Treatment did not lead to clinical improvement. CONCLUSIONS: In a patient with acute flaccid myelitis, HEV-D68 infection should be ruled out. Cases in which the virus was not detected were considered as "false negatives" as samples were collected late in course of the disease. The lack of response to anti-inflammatory and immunomodulatory treatment suggests a direct viral mechanism. This study is to our knowledge the first on an HEV-D68-infection-related cluster in Latin America.