Familial amyloid polyneuropathy: a proposal for an epidemiological study through the creation of a virtual platform / Polineuropatia amiloidótica familiar: uma proposta de estudo epidemiológico por meio da criação de uma plataforma virtual

Amyloidosis are characterized by mutations in the gene coding for transthyretin (TTR), located on chromosome 18. TTR is a set of four 127-aminoacid polypeptides structured as homotetrameric protein of 56 kDa with a secondary ß sheet structure. It plays the role of thyroxin (T4) carrier, and has a binding domain for retinol (vitamin A). It is synthesized in the liver, although a small quantity is also produced by the choroid plexus, and retinal cells. Mutations of this gene result in loss of tetramer stability. Insoluble amyloid fibrils (AF) are formed and deposited in tissues and organs. The abnormal aggregation of TTR protein trigger several syndromes, such as familial amyloid polyneuropathy (FAP-TTR), cardiomyopathies (CMP), and senile systemic amyloidosis (SSA). It is estimated there are 5,000 to 10,000 cases of FAP-TTR globally. OBJECTIVE: The study intends to develop an online platform for the diagnosis of FAP-TTR. The aim is to facilitate the diagnosis process and promote a tool for epidemiological study. METHODS: The project was based on a literature review featuring clinical and epidemiological evidence for the development of a practical platform (applied research). RESULTS: It was elaborated a platform containing a questionnaire to allow a more dynamic, cheaper, and efficient operation, mediated by a better characterization of the disease to enable its early diagnosis. CONCLUSION: The platform might become a valuable resource for the characterization, diagnosis, and future epidemiological study of FAP-TTR

As amiloidoses se caracterizam por mutações no gene codificante da transtirretina (TTR) no cromossomo 18. A proteína TTR compõe-se de uma corrente de polipeptídios de 127 resíduos, que constituem uma proteína homotetramérica de 56kDa com estrutura secundária de folha ß, que serve como proteína de deslocamento para a tiroxina (T4), e uma proteína de ligação ao retinol (vitamina A). O principal local de produção dessa proteína é o fígado, embora uma pequena quantidade seja produzida pelo plexo coroide e pelas células retinianas. O gene codificante da TTR (18q11.2-12) é pequeno (7 kb) e contém quatro éxons. As mutações convertem-se em perda do equilíbrio do tetrâmero proteico. Surgem assim, fibrilas amiloides (FA) em cadeias não ramificadas de 10 a 12 nm de diâmetro e fibrilas indissolúveis, que se condensam nos tecidos e órgãos. As síndromes concernentes ao acúmulo da proteína TTR são: polineuropatia amiloidótica familiar (PAFTTR), miocardiopatias (MCP) e amiloidose sistêmica senil (ASS). Estimativa recente relatou a existência de 5.000 a 10.000 casos de PAFTTR no mundo. OBJETIVO: O estudo objetiva elaborar uma plataforma de diagnóstico PAFTTR on-line para auxiliar como ferramenta de contribuição para o estudo da epidemiologia e facilitar o diagnóstico. MÉTODOS: O projeto baseou-se em uma pesquisa bibliográfica capaz de levantar evidências clínicas e epidemiológicas na elaboração de uma plataforma facilitadora (pesquisa aplicada). RESULTADOS: O resultado alcançado foi a elaboração da plataforma contendo um questionário, que tornará o trabalho dos profissionais mais dinâmico, barato e eficiente, caracterizando melhor a doença e promovendo um diagnóstico precoce. CONCLUSÃO: A plataforma poderá tornar-se recurso valioso para caracterização, diagnóstico e futuro estudo epidemiológico da PAF-TTR

Microcephaly and arthrogryposis multiplex congenita: The full-blown CNS spectrum in newborns with ZIKV infection.

The recent alarming statements concerning the newborn ZIKV-induced microcephaly epidemics in the Northeast of Brazil, released by the Brazilian Ministry of Health, as well as important international health agencies, such as the World Health Organization and the Pan American Health Organization, raised many "why and how" questions so far, that will hopefully be scientifically answered, as more researches in that regard come up in the long term. In this paper, we describe another potentially ZIKV-induced central nervous system and musculoskeletal disorder that has accompanied microcephaly in these children: atrhogryposis multiplex congenita. The goal is to bring up some hypotheses for possible underlying molecular mechanisms based on published data taken from animal models, such as ovine and cattle, which once infected by other types of arboviroses and viruses that also belong to the Flaviviridae family, presented, too, with the full-blown CNS spectrum of malformations at birth.

Zika Virus Infection in the Elderly: Possible Relationship with Guillain-Barré Syndrome.

The Zika virus (ZIKV) outbreak in French Polynesia, in 2013, and in Brazil, in 2015, was correlated with neurological complications, which comprised, among others, congenital microcephaly and Guillain-Barré syndrome (GBS), which includes a group of acute autoimmune neuropathies generally reported after respiratory or gastrointestinal infectious diseases. Despite being relatively rare, the incidence rate of GBS rises with age, which makes GBS more frequent in the elderly, in whom it is also a more severe disease with slower recovery than in younger patients. Different forms of GBS have been described having diagnostic confirmation of a previous infection with the ZIKV virus. Although we do not have enough evidence that elderly people are a particularly susceptible population to developing GBS following ZIKV infection, this is plausible. We should consider this possibility, particularly taking into account that aging subjects are more susceptible to infections. In this context, a deeper understanding of how the immune system in the elderly functions in relation to ZIKV infection is necessary, as well as an understanding of what kind of alterations of the nervous system such an infection triggers in the elderly, beyond GBS. This will be relevant for better therapeutic interventions and for designing vaccine candidates that can be applied in an aging population, particularly those prone to develop ZIKV-induced autoimmunity.

Excessive daytime sleepiness and epilepsy: a systematic review.

Background. Sleep complaints are common in patients with epilepsy (PWE). Excessive daytime sleepiness (EDS) is one of the most reported complaints and its impact is still a matter of debate. Objective. Evaluate the relationship between EDS and epilepsy, with emphasis on prevalence, assessment, and causes. Methods. A systematic review on PubMed database in the last 10 years (2002 to 2012). The search returned 53 articles and 34 were considered relevant. After citation analysis, 3 more articles were included. Results. Most studies were cross-sectional and questionnaire based. 14 papers addressed EDS as the primary endpoint. 14 adult and 3 children studies used subjective and objective analysis as methodology. The number of studies increased throughout the decade, with 21 in the last 5 years. Adult studies represent almost three times the number of children studies. EDS prevalence in PWE varies from 10 to 47.5%. Prevalence was higher in developing countries. Conclusion. EDS seems to be related more frequently to undiagnosed sleep disorders than to epilepsy-related factors, and although it affects the quality of life of PWE, it can be improved by treating comorbid primary sleep disorders.