Currently, the most common clinical scores for rating the disease severity are the Scale for the
Assessment and Rating of Ataxia (SARA). However, the SARA score cannot be used to evaluate pre-manifest individuals and their small effect size would require large numbers of patients in clinical trials, which is an issue due to the scarcity of SCA.
As gene-based therapies are showing promise in preventing or reversing SCA pathophysiology, there is a need for biomarkers with effect sizes greater than clinical scores, which can be used in trials on small sample sizes.
Clinical scores worsened as atrophy increased over time. However, atrophy of cerebellum and pons showed very large effect sizes compared to clinical scores. Imaging was sensitive to microstructural cross-sectional differences that were not captured by conventional methods. Automated imaging also showed larger effect sizes than manual imaging.
This study showed that volumetry (imaging) outperformed clinical scores to measure disease progression in SCA1, SCA2, SCA3 and SCA7.
Therefore, the researchers advocate the use of volumetric biomarkers in therapeutic trials of autosomal dominant ataxias. In addition, automated imaging showed larger effect size than manual imaging to detect cross-sectional microstructural alterations in patients relative to controls.
Autosomal dominant cerebellar ataxias: Imaging biomarkers with high effect sizes, Isaac M. Adanyeguh et al., Neuroimage Clin. 2018; 19: 858–867.
Published online 2018 Jun 14. doi: 10.1016/j.nicl.2018.06.011