RESUMO
Tuberous sclerosis complex (TSC) is a neurogenetic disorder leading to epilepsy, developmental delay, and neurobehavioral dysfunction. The syndrome is caused by pathogenic variants in TSC1 (coding for hamartin) or TSC2 (coding for tuberin). Recently, we reported a progressive frontotemporal dementia-like clinical syndrome in a patient with a mutation in TSC1, but the neuropathological changes seen in adults with TSC with or without dementia have yet to be systematically explored. Here, we examined neuropathological findings in adults with TSC (n = 11) aged 30-58 years and compared them to age-matched patients with epilepsy unrelated to TSC (n = 9) and non-neurological controls (n = 10). In 3 of 11 subjects with TSC, we observed a neurofibrillary tangle-predominant "TSC tauopathy" not seen in epilepsy or non-neurological controls. This tauopathy was observed in the absence of pathological amyloid beta, TDP-43, or alpha-synuclein deposition. The neurofibrillary tangles in TSC tauopathy showed a unique pattern of post-translational modifications, with apparent differences between TSC1 and TSC2 mutation carriers. Tau acetylation (K274, K343) was prominent in both TSC1 and TSC2, whereas tau phosphorylation at a common phospho-epitope (S202) was observed only in TSC2. TSC tauopathy was observed in selected neocortical, limbic, subcortical, and brainstem sites and showed a 3-repeat greater than 4-repeat tau isoform pattern in both TSC1 and TSC2 mutation carriers, but no tangles were immunolabeled with MC1 or p62 antibodies. The findings suggest that individuals with TSC are at risk for a unique tauopathy in mid-life and that tauopathy pathogenesis may involve TSC1, TSC2, and related molecular pathways.
Assuntos
Epilepsia , Tauopatias , Esclerose Tuberosa , Adulto , Humanos , Proteínas Supressoras de Tumor/genética , Esclerose Tuberosa/genética , Esclerose Tuberosa/metabolismo , Peptídeos beta-Amiloides/genética , Mutação/genética , Epilepsia/genética , Tauopatias/genéticaRESUMO
El presente estudio es una investigación que responde al paradigma interpretativo, de tipo exploratorio y metodología cualitativa, desde el enfoque fenomenológico. Esta investigación fue realizada en Santiago de Chile el año 2013 en un centro de acupuntura ubicado en la comuna de Independencia. Se realizaron siete entrevistas semi estructuradas a personas en terapia de acupuntura, obteniéndose las siguientes conclusiones: La acupuntura posee buena aceptación por parte de los usuarios, generando una opinión positiva hacia el uso de esta de terapia, debido a que se obtiene en la mayoría de los casos una resolución al problema de salud por el cual consultaron. Siendo considerada como un complemento o una alternativa, confiable y resolutiva de las patologías que presentan los entrevistados, a la medicina convencional.