RESUMO
Autistic spectrum disorders affect one out of every 68 persons, with a 4:1 dominance in males. Since they are dysfunctions rather than irreversible injuries to the central nervous system, which can be attributed to deficits in the neuronal networks and synaptogenesis and are modifiable thanks to the plasticity of the brain, starting therapy as early as possible is essential for more favourable progress. Very few treatments are backed by solid scientific evidence. We will analyse the therapeutic approaches oriented towards improving autism spectrum disorders which showed a clinical improvement that can be related to neurophysiological or functional changes in the central nervous system. We will classify the behavioural educational treatments and those in the research phase into a hierarchy, highlighting the neurogenetic entities with a high prevalence of autism, in which their pathophysiology and molecular base are known, that attempt to modify the consequences of those alterations by means of pharmacological agents. These entities include fragile X syndrome (GABAergic and metabotropic glutamate receptor inhibitors), tuberous sclerosis (mTOR inhibitors), Phelan-McDermid syndrome and Rett syndrome (insulin-like growth factor 1 inhibitors). Oxytocin, which has been shown to improve social cognition in persons with autism spectrum disorders, is analysed separately.
TITLE: Abordajes terapeuticos en los trastornos del espectro autista.Los trastornos del espectro autista afectan a una de cada 68 personas, con predominio de 4 a 1 en varones. Por tratarse de disfunciones y no lesiones irreversibles del sistema nervioso central, atribuibles a defectos en las redes neuronales y la sinaptogenesis, modificables gracias a la plasticidad cerebral, la precocidad en el inicio terapeutico es fundamental para una mejor evolucion. Son pocos los tratamientos que cuentan con clara evidencia cientifica. Analizaremos abordajes terapeuticos orientados a mejorar los trastornos del espectro autista que demostraron una mejoria clinica relacionable a cambios neurofisiologicos o funcionales en el sistema nervioso central. Jerarquizaremos los tratamientos educativos conductuales y aquellos en etapa de investigacion, puntualizando las entidades neurogeneticas con alta prevalencia de autismo, en las cuales se conoce su fisiopatologia y base molecular, que intentan modificar a traves de farmacos las consecuencias de dichas alteraciones, incluyendo el sindrome X fragil (gabergicos e inhibidores del receptor metabotropico del glutamato), la esclerosis tuberosa (inhibidores del mTOR), el sindrome de Phelan-McDermid y el sindrome de Rett (inhibidores del desarrollo insulinico-1). Separadamente se analiza la oxitocina, que ha demostrando una mejoria en la cognicion social en personas con trastornos del espectro autista.
Assuntos
Transtorno do Espectro Autista/terapia , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , MasculinoRESUMO
Paroxysmal events in childhood are a challenge for pediatric neurologists, given its highly heterogeneous clinical manifestations, often difficult to distinguish between phenomena of epileptic seizure or not. The non-epileptic paroxysmal episodes are neurological phenomena, with motor, sensory symptoms, and/or sensory impairments, with or without involvement of consciousness, epileptic phenomena unrelated, so no electroencephalographic correlative expression between or during episodes. From the clinical point of view can be classified into four groups: motor phenomena, syncope, migraine (and associated conditions) and acute psychiatric symptoms. In this paper we analyze paroxysmal motor phenomena in awake children, dividing them according to their clinical manifestations: extrapyramidal episodes (paroxysmal kinesiogenic, non kinesiogenic and not related to exercise dyskinesias, Dopa responsive dystonia) and similar symptoms of dystonia (Sandifer syndrome); manifestations of startle (hyperekplexia); episodic eye and head movements (benign paroxysmal tonic upward gaze nistagmus deviation); episodic ataxia (familial episodic ataxias, paroxysmal benign vertigo); stereotyped and phenomena of self-gratification; and myoclonic events (benign myoclonus of early infancy). The detection of these syndromes will, in many cases, allow an adequate genetic counseling, initiate a specific treatment and avoid unnecessary additional studies. Molecular studies have demonstrated a real relationship between epileptic and non-epileptic basis of many of these entities and surely the identification of the molecular basis and understanding of the pathophysiological mechanisms in many of them allow us, in the near future will benefit our patients.
TITLE: Fenomenos paroxisticos no epilepticos motores en vigilia en la infancia.Los eventos paroxisticos en la infancia son un desafio para los neuropediatras por sus manifestaciones clinicas altamente heterogeneas, muchas veces dificiles de diferenciar entre fenomenos de origen epileptico o no epileptico. Los fenomenos paroxisticos no epilepticos son fenomenos neurologicos, episodicos, con sintomas motores, sensitivos o sensoriales, con o sin afectacion de la conciencia, no relacionados a fenomenos epilepticos, por lo cual no tienen correlato de expresion electroencefalografica entre o durante los episodios. Desde el punto de vista clinico, podemos clasificarlos en cuatro grandes grupos: fenomenos motores, sincopes, migraña (y condiciones asociadas) y cuadros psiquiatricos agudos. En este trabajo se analizan los fenomenos paroxisticos motores en vigilia, dividiendolos de acuerdo a sus manifestaciones clinicas en: episodios extrapiramidales (discinesias paroxisticas cinesiogenicas, no cinesiogenicas y relacionadas con el ejercicio, distonia sensible a levodopa) y cuadros simil distonia (sindrome de Sandifer); manifestaciones de sobresalto (hiperecplexia); movimientos episodicos oculares y cefalicos (desviacion tonica paroxistica de la mirada hacia arriba); ataxia episodica (ataxias episodicas autosomicas familiares y vertigo paroxistico benigno); estereotipias y fenomenos de autogratificacion; y eventos mioclonicos (mioclonias benignas de la infancia temprana). La deteccion de estos sindromes permitira, en muchos casos, realizar un asesoramiento genetico adecuado, instaurar un tratamiento especifico y evitar estudios complementarios innecesarios. Los estudios moleculares han demostrado una relacion entre las bases epilepticas y no epilepticas en muchas de estas entidades. Seguramente la identificacion de los aspectos moleculares y la comprension de los mecanismos fisiopatologicos de muchas de ellas permitiran en un futuro no muy lejano tratamientos especificos que beneficiaran a los pacientes.
Assuntos
Discinesias/fisiopatologia , Mioclonia/fisiopatologia , Convulsões/fisiopatologia , Vigília/fisiologia , Anticonvulsivantes/uso terapêutico , Ataxia/diagnóstico , Ataxia/etiologia , Ataxia/fisiopatologia , Vertigem Posicional Paroxística Benigna , Criança , Pré-Escolar , Diagnóstico Diferencial , Discinesias/diagnóstico , Discinesias/etiologia , Distonia/diagnóstico , Distonia/tratamento farmacológico , Distonia/fisiopatologia , Eletroencefalografia , Exercício Físico , Humanos , Transtornos dos Movimentos/diagnóstico , Transtornos dos Movimentos/tratamento farmacológico , Transtornos dos Movimentos/fisiopatologia , Mioclonia/diagnóstico , Mioclonia/etiologia , Convulsões/diagnóstico , Convulsões/tratamento farmacológico , Convulsões/genética , Autoestimulação , Transtorno de Movimento Estereotipado/diagnóstico , Transtorno de Movimento Estereotipado/fisiopatologia , Rigidez Muscular Espasmódica/diagnóstico , Rigidez Muscular Espasmódica/fisiopatologia , Vertigem/diagnósticoRESUMO
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.
Assuntos
Anormalidades Congênitas/diagnóstico , Doenças Genéticas Inatas/diagnóstico , Triagem Neonatal , Transtornos Cromossômicos/diagnóstico , Transtornos Cromossômicos/genética , Anormalidades Congênitas/genética , Humanos , Recém-Nascido , Deficiência Intelectual/diagnóstico , Deficiência Intelectual/genética , SíndromeRESUMO
La presencia de un cuadro neurológico neonatal asociado o no a dismorfias o a un fenotipo particular puede responder a diversas causas a) Prenatales: infecciosas (Grupo TORCH), agentes tóxicos o teratogénicos (alcohol, cocaína, antiepilépticos, inhalantes como el tolueno, etc.), defectos vasculares o anomalías genéticas b) Perinatales: cuadros hipóxico isquémicos, infecciones o trastornos metabólicos, entre otros. En este trabajo analizaremos aquellas entidades de origen genético reconocibles en el período neonatal por su fenotipo, las cuales deben incluirse entre los diagnósticos diferenciales frente a un niño con compromiso neurológico. Con el objeto de facilitar el reconocimiento de estas entidades las dividiremos de acuerdo al fenotipo más destacado u orientador, presente en el momento del nacimiento dividiéndolas en 2 grandes grupos: 1) Génicas, en las que incluimos: Síndromes con facies características y malformaciones en los miembros; Síndromes de sobrecrecimiento; Síndromes con déficit del crecimiento prenatal; Síndromes neuro-ectodérmicos; Síndromes con facies características con compromiso ocular y Síndromes con facies características (incluyendo, en las que lo tienen, su número del MIM) y 2) Cromosómicas (anomalías en los autosomas: de número; en mosaico; deleciones y anomalías en los cromosomas sexuales). El reconocimiento a través del fenotipo de encefalopatías congénitas de origen genético es de gran importancia ya que su identificación permitirá: Orientar estudios diagnósticos específicos; evitar prácticas cruentas y/o costosas, inútiles si el diagnóstico clínico es por sí orientador; proveer el adecuado asesoramiento genético familiar y controlar evolutivamente las posibles complicaciones.
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.