Clinical and regulatory acceptance of new molecular therapies for degenerative ataxias may benefit tremendously from ecologically valid outcomes that reflect changes in ataxia severity in patients’ daily lives. For a longitudinal study, researchers sought to identify quantitative motor biomarkers in degenerative ataxias turning motions that are sensitive to alterations both longitudinally and at the preataxic stage. A cross-sectional (n=30) and longitudinal (n=14, 1-year interval) observational analysis of degenerative cerebellar disease (including eight preataxic mutation carriers) was conducted in comparison to 23 healthy controls. Three body-worn inertial sensors analyzed turning motions in three conditions: instructional laboratory evaluation supervised free walking and unsupervised real-life movements. 

Measures that quantified dynamic balance during turning, such as lateral velocity change (LVC) and outward acceleration, but not general turning measures like speed, allowed distinguishing ataxic from healthy subjects in real life (effect size δ=0.68), with LVC also distinguishing preataxic from healthy subjects (δ=0.53). In addition, LVC was shown to be substantially linked with clinical ataxia severity (SARA score, effect size ρ=0.79) and patient-reported balance confidence (activity-specific balance confidence scale [ABC] score, ρ=0.66). Furthermore, LVC in real life—but not general turning measures or the SARA score—allowed identifying substantial longitudinal change with a large effect size (rprb = 0.66) in a 1-year follow-up.

Turning measures allowed for capturing precise alterations in dynamic balance in degenerative ataxia in real-time, with a high sensitivity to longitudinal variations in ataxia severity and the preataxic stage. They thus revealed potential ecologically valid motor indicators, even in the early stages of degenerative cerebellar illness, which are highly treatment-relevant.

Reference:movementdisorders.onlinelibrary.wiley.com/doi/10.1002/mds.28930