Structural and Functional Changes in the Cerebellum in Sporadic Ataxias

Abstract

Sporadic ataxia is a group of progressive neurodegenerative diseases that can be subdivided into two groups, sporadic adult onset ataxia (SAOA), and the cerebellar type of multiple system atrophy (MSA-C). In the first years after ataxia onset, a reliable distinction between MSA-C and SAOA is often not possible. In particular, some SAOA conditions may turn to MSA-C, and it is known that the conversion becomes very unlikely when a patient with SAOA has a duration of illness longer than 10 years. In this thesis, MSA-C vs. SAOA>10y (defined as SAOA patients with a disease duration longer than 10 years) were compared in an attempt to identify the essential difference between the two conditions. To this end, 16 patients with MSA-C, 13 patients with SAOA>10y and 49 healthy controls were included in this thesis. Chapter 1 first introduces the reader to the concept of sporadic ataxias and gives an overview of MSA-C and SAOA. This is followed by a review of the current state of knowledge of how neuroimaging technology aids understanding of sporadic ataxias. Chapter 2 outlines the general methodologies used for the presented studies. Chapter 3 contains four study results. In study 1, the structural changes of the cerebellum in two ataxia groups were examined to show abnormal gray matter volume in the bilateral anterior part and right posterior part of the cerebellum in both groups and an additional atrophy in vermis cerebellum in the SAOA>10y group. In study 2, the intracerebellar functional connectivity affected by local atrophy was investigated in the two sporadic ataxias by the amplitude of low-frequency fluctuation and degree centrality. An intact functional connectivity pattern was observed in the atrophic cerebellum in the MSA-C and SAOA groups, the atrophic cerebellum being characterized by high ALFF and high DC compared with non-atrophic cerebellum. In study 3, the topological features of the functional cerebellar network were assessed by graph theory analysis. It was found that a well-organized small-world network organization and intact global and regional properties existed in the functional cerebellar system in the ataxia groups. In study 4, the connectivity between different cerebellar parts and cerebral regions was explored, taking every functional cerebellar module as a region of interest. It was observed that the activities of cerebellar modules were positively correlated with the thalamus and negatively connected to the postcentral and precentral gyrus in the healthy group. When compared with the HC group, altered connections between the cerebellum and the visual cortex, the motor cortex and the frontal cortex were found in the MSA-C but not in the SAOA>10y groups. Chapter 4 contains a summary discussion of all four studies, as well as discussing the limitations of the current researches and offering an outlook on future research perspectives.