Navegando por Palavras-chave "Ataxia Cerebelar"
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- ItemAcesso aberto (Open Access)Aspectos clínicos e genéticos, avaliação cognitiva e neuroimagem em pacientes com Ataxia autossômica recessiva relacionada ao gene SYNE1(Universidade Federal de São Paulo (UNIFESP), 2019-03-28) Gama, Maria Thereza Drumond [UNIFESP]; Pedroso, Jose Luiz [UNIFESP]; http://lattes.cnpq.br/9366916338480574; http://lattes.cnpq.br/1344322795907776; Universidade Federal de São Paulo (UNIFESP)BACKGROUND: Cerebellar ataxias are a heterogenous group of diseases that can affect individuals of all ages and are characterized by degeneration of the cerebellum and cerebellar pathways. The most common genetic forms of ataxias are those caused by abnormal expansion of trinucleotides, whose genetic tests are already widely used. With the advancement of diagnostic techniques, many genes could be identified as causing undetermined ataxias, as the case of ataxia related to the mutation of the SYNE1 gene, wich was first described in 2007 in a Canadian population. OBJECTIVES: In order to adress different objectives this clinical protocol is divided into sub-studies as follows: Study 1– to asses clinically and genetically diagnosed patients with ataxia related to SYNE1 in the Brazilian population.Study 2– to perform a neuropsychological and psychiatric analysis in these patients. Study 3– to perform multimodal neuroimaging analyses and investigate cerebelar and potential extra-cerebellar changes in SYNE1 ataxia. METHODOLOGY: Patients aged 10 to 40 years with cerebellar ataxia and retained reflexes were selected. The clinical protocol consisted of: clinical evaluation, ataxia scales (ICARS e SARA), molecular test, neuropsychological and specific psychiatric analyses and multimodal neuroimaging protocol. Specific statistical analysis is described in each study separately. RESULTS: Study 1: it was found a frequency of 10.25% of the disease in this sample of patients and the clinical phenotype varied from the classical cerebellar form to the complex forms, wich has association with motor neuron disease. Study 2 - the following domains of cognition were altered: executive function, attention and processing speed. In psychiatric analyses, a mild degree of anxiety and difficulty in the abstraction of thought was observed. Study 3 – it was found a cerebellar involvement (cortical atrophy and alteration of the white matter), reduction of cortical thickness in the primary motor area and pre-motor area and degeneration of the cortico-spinal tract in the motor cortex, internal capsule and cerebral peduncle, similar findings to those found in motor neuron disease. CONCLUSION: This study was the first to demonstrate the frequency of cerebellar ataxia related to the mutation of the SYNE1 gene in the Brazilian population. The phenotypic variability was confirmed, as was described in other international studies. Some cognitive domains were involved, wich corroborates the role of the cerebellum in cognition. The neuroimaging findings were consistent with the clinical heterogeneity described.
- ItemAcesso aberto (Open Access)Avaliação clínica, genética, radiológica e da arquitetura retiniana em pacientes com ataxia relacionada ao gene SACS(Universidade Federal de São Paulo (UNIFESP), 2019-04-25) Rezende Filho, Flavio Moura [UNIFESP]; Barsottini, Orlando Graziani Povoas [UNIFESP]; http://lattes.cnpq.br/0768140730368272; http://lattes.cnpq.br/6551090058120202; Universidade Federal de São Paulo (UNIFESP)BACKGROUND: Cerebellar ataxia is characterized by loss of balance and coordination, and is found in several neurological conditions. This group of disorders is very diverse in clinical presentations and etiopathogenesis, and includes neurovascular, inflammatory, infectious, neurodegenerative and hereditary diseases. Genetic defects are an important cause of ataxia. The progress in molecular diagnosis techniques has allowed the identification of causative genes and characterization of new forms of ataxia, including the autosomal recessive spastic ataxia of CharlevoixSaguenay (ARSACS), described in 1978 in French-Canadian families. The causative gene of this disorder, SACS, was identified in 2000 and this allowed molecular confirmation in several regions of the world. Thickening in the retinal nerve fiber layer (RNFL) in optical coherence tomography (OCT) is a hallmark of ARSACS, which distinguishes it from other ataxias. Many aspects of the pathogenesis of ARSACS are not clear and large series of Brazilian patients have not been published. OBJECTIVES: This thesis is divided in two studies, with the following objectives: Study 1 - To evaluate the clinical, genetic, neuroimaging and ophthalmological profile of Brazilian patients with ARSACS. Study 2 - To analyze qualitatively the retinal architecture of 28 ARSACS cases. METHODS: In the Study 1, we included 13 consecutive cases of spastic ataxia harboring two SACS variants and performed detailed neurological assessment, neuroimage study and ophthalmological evaluation, and applied scales to quantify ataxia severity. Brazilian patients phenotype was compared to the largest series published. The Study 2 investigated the retinal architecture of 28 ARSACS cases using fundoscopy and perifoveal spectral domain OCT scans. RESULTS: Study 1 - The phenotype of Brazilian patients with ARSACS is characterized in most cases by spastic ataxia with onset in the first decade of life. Abnormalities in neuroimaging and retinal architecture occurred in the majority. Study 2 - Patients with ARSACS presented specific findings in qualitative analysis of retinal architecture. We identified peripapillary striations, a papillomacular fold, the saw-tooth sign and foveal hypoplasia in OCT. CONCLUSIONS: Study 1 is the first to evaluate systematically the phenotype of ARSACS in a large Brazilian cohort and confirmed the importance of neuroimaging and OCT in the work-up of recessive ataxias. Study 2 revealed specific signs of ARSACS in qualitative analysis of retinal architecture and demonstrated ARSACS causes foveal hypoplasia, suggesting a neurodevelopmental component in its pathogenesis.
- ItemSomente MetadadadosNeuroimagem com utilização com sequência de tensor de difusão para avaliação da via piramidal em pacientes com ataxia espinocerebelar tipo 3(Universidade Federal de São Paulo (UNIFESP), 2020-10-29) Inada, Bruno Shigueo Yonekura [UNIFESP]; Pedroso, Jose Luiz [UNIFESP]; Universidade Federal de São PauloObjective: Evaluate the pyramidal tract of patients with spinocerebellar ataxia type 3 and correlate with the scale for the assessment and rating of ataxia (SARA). Methods: This study used diffusion tensor imaging to access the pyramidal tract of 120 spinocerebellar ataxia type 3 patients from 2 different health centers: 29 patients from Ataxia outpatient clinic at UNIFESP hospital and 91 patients from Neurogenetic outpatient clinic at UNICAMP hospital that underwent a 1.5 Tesla and 3,0 Tesla magnetic resonance image, respectively. We selected 120 age and gender-matched healthy individuals. Fractional anisotropy, mean diffusivity, radiation diffusivity and axial diffusivity values were obtained and correlated with the scale for the assessment and rating of ataxia. Results: In group 1, a significant reduction was found only in the fractional anisotropy (FA) values in the pre-central gyrus bilaterally. In group 2 there was a significant reduction in the FA values and a significant increase in the values of mean diffusivity (MD), radial diffusivity (RD) and axial diffusivity (AD) in corticospinal tract, except for the MD and AD values in the right precentral gyrus and AD values in the left precentral gyrus, bilateral superior corona radiata and the right cerebral peduncle. Moderate negative correlation was found between the FA values on the entire length of the corticospinal tract of patients in group 2 and SARA, in addition to a moderate positive correlation between the values of MD and RD on the entire length of the corticospinal tract of patients in group 2 and SARA. Conclusions: we demonstrated the presence of a microstructural lesion in the pyramidal tract of SCA3 patients, which may explain the high frequency of pyramidal signs in these patients, in addition to the moderate correlation with the scale for the assessment and rating of ataxia (SARA). In addition, we observed that the alteration in the corticospinal tract occurs more sharply in the caudal segment (base of the bridge) than in the cranial segment (pre-central gyrus), which may suggest a “dying back” degeneration mechanism.