Movement disorders: Digitized gait biomarkers can capture longitudinal changes in type 3 cerebellar ataxia over a 1-year period

With the advent of drugs to treat the disease of degenerative ataxia, sensitive exercise biomarkers are essential
.
In multiple cross-sectional studies, gait measurements, including stride variability and body swing, have shown sensitivity to ataxia severity, associated
with clinical ataxia scores.
However, this correlation is strongly influenced by the range of disease severity: for cohorts containing various disease stages, many gait measurements, including non-specific measurements like velocity, show correlation with disease severity, often driven
primarily by subjects at both ends of the disease severity spectrum.

Figure 1: Cover art of the paper

In intervention trials, the goal of evaluating exercise biomarkers varied qualitatively, i.
e.
, to quantify
individual changes in a short period of time (e.
g.
, 1 year).
To be effective biomarkers of progression, these gait measurements must demonstrate their sensitivity
to individual longitudinal changes over the realistic time span of the intervention trial.

Winfried Ilg et al.
of the University of Tübingen in Germany presented the first longitudinal study
in a multicenter spinal cerebellar ataxia (SCA) cohort.
They demonstrated that digital exercise biomarkers can capture longitudinal changes over a 1-year period, and this sensitivity to changes is superior to clinical ataxia scores
.

In some cross-sectional studies, measurements of gait variability and body swing in gait have been shown to correlate
with the severity of clinical ataxia.
However, to be an effective progression biomarker, these gait measurements must demonstrate their sensitivity to strongly capture longitudinal changes, preferably in a short period of time (e.
g.
, 1 year
).

Figure 2: Graph of the paper results

They proposed the first longitudinal gait analysis study
of polycentric spinocerebellar ataxia.
They performed a comprehensive cross-sectional (n=28) and longitudinal (1-year interval, n=17) analysis
of spinocerebellar ataxia type 3 subjects, including 7 anterior axis mutation carriers.

Longitudinal analysis showed a significant change in gait measurements during baseline and 1-year follow-up, with a high effect size (step change rate
.
P = 0.
01, effect size rprb = 0.
66; side swing: P = 0.
007, rprb = 0.
73).

Laterally swinging sample size estimates indicate that the cohort size required to detect a 50% reduction in natural progression is n = 43, compared to n = 240
for the Clinical Ataxia Score Ataxia Evaluation Scale (SARA).

The significance of this study lies in the discovery that data gait measures provide promising motor biomarkers
for upcoming interventional studies.