Neuroimagem na ataxia de Friedreich = novas abordagens e aplicações clínicas = Neuroimaging in Friedreich's ataxia = new approaches and clinical aplication

Rezende, Thiago Junqueira Ribeiro de; Advisor: França Junior, Marcondes Cavalcante. TESE DIGITAL (2017)(POR)

Abstract: Friedreich¿s ataxia (FRDA) is the most common autosomal-recessive ataxia worldwide; it is characterized by early onset, sensory abnormalities and slowly progressive ataxia. Besides that, most of neuroimaging studies have been focused only in infratentorial structures of adult patients. Furthermore, studies comparing different phenotypes of disease does not exist. Therefore, the objective of this study is to assess, using multimodal magnetic (MRI) resonance imaging, patients with Friedreich ataxia to better comprehend the progression of brain damage, to identify the pattern of damage across disease phenotypes, to identify areas with abnormal iron deposits in the brain and to characterize the structures initially damaged in early disease stages. To accomplish that, we enrolled 25 adult patients with classical FRDA, 13 patients with late-onset FRDA and 12 pediatric patients. The FARS scale was employed to quantify the disease severity. To assess the structural damage in gray and white matter, we acquired T1-weighted, T2-weighted and DTI images of the brain. To evaluate these images, we used the following tools: FreeSurfer, T1 MultiAtlas, SPM, DTI MultiAtlas, SpineSeg and TBSS. After group comparisons, there was widespread microstructural damage in the cerebral white matter, including cerebellar peduncles, corpus callosum and pyramidal tracts of patients with FRDA. We also found gray matter volumetric reduction in the dentate nuclei of the cerebellum, brainstem and motor cortex. We did not find volumetric reduction over time, but there was progressive white matter microstructural damage in the corpus callosum, pyramidal tracts and superior cerebellar peduncles after 1 year of follow-up. Regarding the disease phenotypes, we found that both classical FRDA and LOFA have similar, but not identical neuroimaging signatures. Although subtle, the structural differences might help to explain the phenotypic differences seen in both conditions. The corticospinal tracts are damaged in both conditions, but more severely in the late-onset FRDA group, which may explain why pyramidal signs are more evident in the latter subgroup. We failed to identify iron deposits in brain regions other than the dentate nuclei of patients with FRDA. Finally, we found that the spinal cord and inferior cerebellar peduncles are the structures compromised in pediatric patients with FRDA.

Iron Sulfur and Molybdenum Cofactor Enzymes Regulate the Drosophila Life Cycle by Controlling Cell Metabolism

Marelja Z, Leimkühler S and Missirlis F (2018); Front. Physiol. 9:50. doi: 10.3389/fphys.2018.00050


Despite general agreement that frataxin is required for a functional nervous system, disagreement has been expressed on the cause, with different authors favoring oxidative stress (Llorens et al., 2007; Anderson et al., 2008; Kondapalli et al., 2008), iron toxicity (Soriano et al., 2013; Navarro et al., 2015), altered mitochondrial metabolism (Navarro et al., 2010; Tricoire et al., 2014; Calap-Quintana et al., 2015; Soriano et al., 2016), sphingolipid signaling (Chen et al., 2016b), and failure to maintain neuronal membrane potential (Shidara and Hollenbeck, 2010). We do not see any contradiction in the various positive claims made in the above-cited literature, whereas the negative claim that is often repeated—refuting a role for oxidative stress in explaining the phenotypes—normally arises because of failure to rescue the phenotypes with some transgenes as opposed to others.