RESUMEN
BACKGROUND: The natural history of neurodegeneration in spinocerebellar ataxia type 3/Machado Joseph disease is still unclear. Here, we built a long-term longitudinal clinical and neuroimaging study to address this point. METHODS: Twenty-three patients with spinocerebellar ataxia type 3/Machado Joseph disease and 22 healthy controls underwent 3T MRI twice 5.0 years apart. T1 and diffusion tensor imaging sequences were obtained. We used T1 multiatlas, diffusion tensor imaging multiatlas, SpineSeg, and CERES-SUIT for cerebral gray and white matter, spinal cord and cerebellar analyses, respectively. Clinical severity was assessed with scale for assessment and rating of ataxia. Analysis of covariance evaluated longitudinal between-group changes. Effect sizes were calculated for each significant result. RESULTS: Progressive volumetric abnormalities were most evident in the cerebellum (Lobule X and Crus II; effect size, 2.0), followed by the basal ganglia (effect size, 0.7). The cerebellar peduncles had the largest white-matter diffusivity changes (effect size, 1.29). Scale for assessment and rating of ataxia-related effect size was 0.82. We failed to identify progressive spinal cord abnormalities. CONCLUSIONS: Longitudinal changes in spinocerebellar ataxia type 3/Machado Joseph disease are more evident in the cerebellum and connections, followed by the basal ganglia. © 2020 International Parkinson and Movement Disorder Society.
Asunto(s)
Enfermedad de Machado-Joseph , Ataxias Espinocerebelosas , Cerebelo , Imagen de Difusión Tensora , Humanos , Enfermedad de Machado-Joseph/diagnóstico por imagen , Enfermedad de Machado-Joseph/genética , Imagen por Resonancia Magnética , Ataxias Espinocerebelosas/diagnóstico por imagen , Ataxias Espinocerebelosas/genéticaRESUMEN
Intermediate-length cytosine-adenine-guanine nucleotide repeat expansions in the ATXN2 gene (which encodes for the protein Ataxin-2) have been linked to increased risk for amyotrophic lateral sclerosis (ALS) in different populations. There is no such study in the Brazilian population, which has a mixed ethnic background. We have thus selected 459 patients with ALS (372 Sporadic ALS and 87 Familial ALS) and 468 control subjects from 6 Brazilian centers to investigate this point. We performed polymerase chain reaction to determine the length of the ATXN2 alleles. Polymerase chain reaction products were resolved using capillary electrophoresis on ABI 3500 × l capillary sequencer. We found that ATXN2 intermediate-length expansions (larger than 26 repeats) were associated with an increased risk for ALS (odds ratio = 2.56, 95% confidence interval: 1.29-5.08, p = 0.005). Phenotype in patients with and without ATXN2 expansions was similar. Our findings support the hypothesis that ATXN2 plays an important role in the pathogenesis of ALS also in the Brazilian population.
Asunto(s)
Esclerosis Amiotrófica Lateral/genética , Ataxina-2/genética , Predisposición Genética a la Enfermedad , Expansión de Repetición de Trinucleótido , Brasil , Estudios de Asociación Genética , Humanos , Factores de RiesgoRESUMEN
Parkinson's disease (PD) is an akinetic-rigid disorder characterized by basal ganglia dysfunction and a possible cerebello-thalamo-cortical circuit involvement. This study aims to investigate the pattern of cerebellar involvement in PD and to assess whether it correlates with clinical parameters. MRI scans were acquired from 50 healthy controls (HC) and 63 patients; 44 were classified as tremor-predominant-PD (PDT) and 19 as akinetic/rigidity-predominant-PD (PDAR). We designed an analysis of covariance including the three groups and contrasted as follows: (1) all 63 PD vs HC, (2) PDT vs HC, (3) PDAR vs HC, and (4) PDT vs PDAR. For a precise evaluation of the cerebellum, we used the SUIT tool for voxel-based morphometry. Applying p = 0.001 and extent threshold = 20 voxels, the overall PD group vs HC showed decreased gray matter (GM) in the left lobules VI and crus I. The PDT group showed decreased cerebellar GM when compared with HC at left lobules VI, VIIb, and VIIIa; at right lobules Crus I, VIIb, and VIIIb; and vermal lobules VI and VIIIa. When compared with PDAR, PDT also showed a decrease in the left lobules VIIIa (p < 0.001). There were small clusters of both positive and negative correlation between disease duration and PDT group. The PDAR group showed no cerebellar changes. Our findings support the growing evidence of cerebellar involvement in the pathogenesis of the resting tremor.