The Scale for the Assessment and Rating of Ataxia is a reliable and valid measure of ataxia, making it an appropriate primary outcome measure for clinical trials.

Our study suggests that spinocerebellar ataxia (SCA) 1, SCA2, and SCA3 share a number of common biologic properties, whereas SCA6 is distinct in that its phenotype is more determined by age than by disease-related factors.

Objective: To obtain quantitative data on the progression of the most common spinocerebellar ataxias (SCAs) and identify factors that influence their progression, we initiated the EUROSCA natural history study, a multicentric longitudinal cohort study of 526 patients with SCA1, SCA2, SCA3, or SCA6. We report the results of the 1-and 2-year follow-up visits. Methods:As the primary outcome measure we used the Scale for the Assessment and Rating of Ataxia (SARA, 0-40), and as a secondary measure the Inventory of Non-Ataxia Symptoms (INAS, 0-16) count. Results:The annual increase of the SARA score was greatest in SCA1 (2.18 Ϯ 0.17, mean Ϯ SE) followed by SCA3 (1.61 Ϯ 0.12) and SCA2 (1.40 Ϯ 0.11). SARA progression in SCA6 was slowest and nonlinear (first year: 0.35 Ϯ 0.34, second year: 1.44 Ϯ 0.34). Analysis of the INAS count yielded similar results. Larger expanded repeats and earlier age at onset were associated with faster SARA progression in SCA1 and SCA2. In SCA1, repeat length of the expanded allele had a similar effect on INAS progression. In SCA3, SARA progression was influenced by the disease duration at inclusion, and INAS progression was faster in females.

This study set out to determine whether there is white matter involvement in essential tremor (ET), the most common movement disorder. We collected diffusion MRI and analysed differences in fractional anisotropy (FA) and mean diffusivity (MD) between ET patients and control subjects as markers of white matter integrity. We used both classical ROI-based statistics and whole-brain analysis techniques, including voxel-wise analysis with SPM5 and tract-based spatial statistics (TBSS). Using region of interest (ROI) analysis, we found increased MD bilaterally in the inferior cerebellar peduncles (ICP) and reduced FA in the right-sided ICP of ET patients. Whole-brain analyses with TBSS detected increased MD distributed in both motor and nonmotor white matter fibers of ET patients predominantly in the left parietal white matter, while there were no significant FA differences in these areas between ET patients and controls. Voxel-wise analysis with SPM detected significant increase of MD congruent with the highest probability of difference as detected by TBSS. VBM analysis of T1 images did not detect significant differences in either gray or white matter density between our study groups. In summary, we found evidence for changes in white matter MRI properties in ET. The circumscript pathology of the ICP corroborates the pathogenetic concept of the cerebellum and its projections as key structures for tremor generation in ET. Moreover, increased diffusivity in white matter structures of both hemispheres suggests widespread alterations of fiber integrity in motor and nonmotor networks in ET patients. The underlying cause of the DTI changes observed remains to be elucidated.

The proposed functional measures and their composite SCAFI have favorable properties to assess patients with spinocerebellar ataxia.