Friedreich ataxia clinical outcome measures: natural history evaluation in 410 participants

Abstract

Friedreich ataxia is an autosomal recessive neurodegenerative disorder characterized by ataxia, dysarthria, and areflexia. The authors report the progress of a large international noninterventional cohort (n = 410), tracking the natural history of disease progression using the neurologic examination-based Friedreich Ataxia Rating Scale. The authors analyzed the rate of progression with cross-sectional analysis and longitudinal analysis over a 2-year period. The Friedreich Ataxia Rating Scale captured disease progression when used at 1 and 2 years following initial evaluation, with a lower ratio of standard deviation of change to mean change over 2 years of evaluation. However, modeling of disease progression identified substantial ceiling effects in the Friedreich Ataxia Rating Scale, suggesting this measure is most useful in subjects before maximal deficit is approached.

Figure 1. Change in FARS score with disease duration

Friedreich Ataxia Rating Scale shown as function of disease duration in the subpopulations based on GAA repeat length >600 (A), >300 – 600 (B), and ≤300 (C).

Figure 2. Friedreich Ataxia Rating Scale score transition probabilities

Friedreich Ataxia Rating Scale score transition probabilities are shown as function of Friedreich Ataxia Rating Scale range. All observations are shown in panel (A), and are stratified by GAA repeat length in panel (B).

Figure 3. Average Friedreich Ataxia Rating Scale change in each FARS range

The average Friedreich Ataxia Rating Scale change for participants at different Friedreich Ataxia Rating Scale ranges is shown for all observations in panel (A) and stratified by GAA repeat length in panel (B).