Structural signature in SCA1: clinical correlates, determinants and natural history.

Spinocerebellar ataxia type 1 is an autosomal dominant disorder caused by a CAG repeat expansion in ATXN1, characterized by progressive cerebellar and extracerebellar symptoms. MRI-based studies in SCA1 focused in the cerebellum and connections, but there are few data about supratentorial/spinal damage and its clinical relevance. We have thus designed this multimodal MRI study to uncover the structural signature of SCA1. To accomplish that, a group of 33 patients and 33 age-and gender-matched healthy controls underwent MRI on a 3T scanner. All patients underwent a comprehensive neurological and neuropsychological evaluation. We correlated the structural findings with the clinical features of the disease. In addition, we evaluated the disease progression looking at differences in SCA1 subgroups defined by disease duration. Ataxia and pyramidal signs were the main symptoms. Neuropsychological evaluation disclosed cognitive impairment in 53% with predominant frontotemporal dysfunction. Gray matter analysis unfolded cortical thinning of primary and associative motor areas with more restricted impairment of deep structures. Deep gray matter atrophy was associated with motor handicap and poor cognition skills. White matter integrity loss was diffuse in the brainstem but restricted in supratentorial structures. Cerebellar cortical thinning was found in multiple areas and correlated not only with motor disability but also with verbal fluency. Spinal cord atrophy correlated with motor handicap. Comparison of MRI findings in disease duration-defined subgroups identified a peculiar pattern of progressive degeneration.

Twenty-five years since the identification of the first SCA gene: history, clinical features and perspectives for SCA1.

Spinocerebellar ataxias (SCA) are a clinically and genetically heterogeneous group of monogenic diseases that share ataxia and autosomal dominant inheritance as the core features. An important proportion of SCAs are caused by CAG trinucleotide repeat expansions in the coding region of different genes. In addition to genetic heterogeneity, clinical features transcend motor symptoms, including cognitive, electrophysiological and imaging aspects. Despite all the progress in the past 25 years, the mechanisms that determine how neuronal death is mediated by these unstable expansions are still unclear. The aim of this article is to review, from an historical point of view, the first CAG-related ataxia to be genetically described: SCA 1.

Twenty-five years since the identification of the first SCA gene: history, clinical features and perspectives for SCA1 / Vinte e cinco anos desde a identificação do primeiro gene das SCAs: história, aspectos clínicos e perspectivas para a SCA1

ABSTRACT Spinocerebellar ataxias (SCA) are a clinically and genetically heterogeneous group of monogenic diseases that share ataxia and autosomal dominant inheritance as the core features. An important proportion of SCAs are caused by CAG trinucleotide repeat expansions in the coding region of different genes. In addition to genetic heterogeneity, clinical features transcend motor symptoms, including cognitive, electrophysiological and imaging aspects. Despite all the progress in the past 25 years, the mechanisms that determine how neuronal death is mediated by these unstable expansions are still unclear. The aim of this article is to review, from an historical point of view, the first CAG-related ataxia to be genetically described: SCA 1.

RESUMO As ataxias espinocerebelares (SCA) são um grupo clínico e geneticamente heterogêneo de doenças monogênicas que compartilham ataxia e herança autossômica dominante como características principais. Uma proporção importante de SCAs é causada por expansões de repetição de trinucleotídeos CAG na região de codificação de diferentes genes. Além da heterogeneidade genética, os aspectos clínicos transcendem os sintomas motores, incluindo aspectos cognitivos, eletrofisiológicos e de imagem. Apesar de todo o progresso feito nos últimos 25 anos, os mecanismos que determinam como se dá a morte neuronal mediada por essas expansões instáveis ainda não estão claros. O objetivo deste artigo é revisar, de um ponto de vista histórico, a primeira ataxia geneticamente relacionada com o CAG descrita: SCA 1.

Postpartum patient with thrombosis of mechanical prostheses and acquired supravalvular aortic stenosis.

The blood hypercoagulability in pregnancy increases significantly the incidence of thrombosis of mechanical valves. Acquired supravalvular aortic stenosis is extremely rare. We report the case of an immediate postpartum patient with aortic mechanical prostheses and acquired supravalvular aortic stenosis who underwent emergency heart surgery, with severe hemodynamic instability, using adapted surgical technique for correction of supravalvular stenosis with satisfactory clinical and echocardiography results.

Puérpera com trombose de prótese mecânica e estenose supravalvar aórtica adquirida / Postpartum patient with thrombosis of mechanical prostheses and acquired supravalvular aortic stenosis

A hipercoagulabilidade sanguínea proporcionada na gravidez aumenta consideravelmente a incidência de trombose de valvas mecânicas. A estenose supravalvar aórtica adquirida é extremamente rara. Relata-se o caso de uma puérpera imediata, portadora de prótese mecânica aórtica e estenose supravalvar aórtica adquirida, submetida à cirurgia cardíaca de emergência, com instabilidade hemodinâmica grave, por meio de técnica operatória adaptada para a correção da estenose supravalvar aórtica, com evolução clínica e resultados ecocardiográficos pós-operatórios satisfatórios.

The blood hypercoagulability in pregnancy increases significantly the incidence of thrombosis of mechanical valves. Acquired supravalvular aortic stenosis is extremely rare. We report the case of an immediate postpartum patient with aortic mechanical prostheses and acquired supravalvular aortic stenosis who underwent emergency heart surgery, with severe hemodynamic instability, using adapted surgical technique for correction of supravalvular stenosis with satisfactory clinical and echocardiography results.

Chronic effect of vagotomy in the morphometry of the myenteric plexus of rats' duodenum / Efeito crônico da vagotomia sobre a morfometria do plexo mioentérico do duodeno de ratos

BACKGROUND: The gastrointestinal disorders have been associated with morphological alterations in the myenteric nervous plexus. AIM: To evaluate, through morphometric studies, the chronic effects of the subdiaphragmatic trunk vagotomy on the nervous plexus. METHODS: Fifteen male exemplars of Wistar Rattus novergicus weighing about 150g, distributed into three groups, have been used: control (n=5), Sham (n=5) and vagotomized (n=5). The animals were sacrificed after 30 and 90 days post surgery. Fragments of duodenum were fixed in Bouin solution, embedded into paraffin and stained with HE and PAS. Morphometric analysis was performed by a Carl Zeiss KM 450 image system. The following aspects were observed: the density of nervous cells per linear micrometer (µm) (ND); the area of perikarya (µm²) (NA); the number of satellite cells per µm (SCD); and the number of satellite cells per neuron (SC/N). The averages were compared with the help of "software" program Sigma Plus through two way - ANOVA and Tuckey post-test. RESULTS: Denervation increased SC/N (p<0,05) and NA (p<0,05), in a time-dependent denervation way (p<0,05). However ND and SCD, decreased, which significantly with the animal's age (p<0,001). CONCLUSION: Vagotomy altered the myenteric plexus morphology in a time-dependent way.

RACIONAL: As disfunções gastrintestinais têm sido associadas à alterações morfológicas no plexo nervoso mioentérico. OBJETIVO: Avaliar através do estudo morfométrico, os efeitos crônicos da vagotomia troncular subdiafragmática sobre esse plexo nervoso. MÉTODOS: Foram utilizados 15 exemplares machos de Rattus novergicus da variedade Wistar, com cerca de 150 g, distribuídos nos grupos controle (n=5), Sham (n=5) e vagotomizados (n=5). Os animais foram sacrificados depois de 30 e 90 dias após as operações. Em seguida, fragmentos do duodeno foram fixados em solução de Bouin, incluídos em parafina e corados por HE e PAS. A análise morfométrica foi realizada por meio do sistema de análise de imagem Carl Zeiss KM 450. Foram observados: a densidade de células nervosas por micrômetro linear (µm); a área dos pericários (µm²); o número de células satélites por µm; e o número de células satélites por neurônio. As médias foram comparadas com o auxílio do programa de "software" Sigma Plus através do Two way - ANOVA e do pós-teste de Tukey. RESULTADOS: A desnervação aumentou o número de células satélites por neurônios (p<0,05) e a área média dos pericários (p<0,05), de maneira dependente do tempo de desnervação (p<0,05), mas diminuiu significativamente a densidade de neurônios (p<0,05) e de células satélites (p<0,05) em função da idade (p<0,001). CONCLUSÃO: A vagotomia alterou a morfologia do plexo mioentérico de maneira dependente do tempo.