Responsivity of the fragile X-associated tremor ataxia syndrome rating scale

OBJECTIVE: To determine the responsivity of the Fragile X-Associated Tremor/Ataxia Syndrome (FXTAS) Rating Scale. BACKGROUND: FXTAS is a progressive neurodegenerative disorder characterized by tremor, gait ataxia, and cognitive decline. Validated outcome measures are needed in order to conduct clinical trials to aid the development of therapy for motor and non-motor features, as there are no known treatments for the disease. The FXTAS Rating Scale was designed to measure the motor features in FXTAS, but longitudinal change of the scale has not been evaluated. DESIGN/METHODS: We retrospectively collected FXTAS rating scale scores that were completed on subjects between 2001 and 2012. Subjects were premutation carriers of the fragile X mental retardation1 gene. We assessed the mean change in the rating scale between baseline and follow up using general linear modeling. Change in FXTAS rating scale score was regressed against time, and a summary change score over time was calculated. RESULTS: We identified 67 subjects at baseline and 25 subjects at follow up. Subjects were 64% male, with mean age 68.6 +8.59 years and mean number of CGG repeats of 86.9. Mean follow up time was 38.5 months +41.5 months. The mean change in score from baseline to follow up was + 4.32 points (SD=13.46). This was calculated to be an average monthly change of +0.213 points and an average yearly change of +2.55 points (95% CI was -12.44 to +17.53). CONCLUSIONS: The FXTAS rating scale scores increased from baseline to follow up at approximately two years by 4.32 points, which is consistent with the progressive natural history of FXTAS. Future studies that incorporate a standardized follow up interval and a larger sample size would help to better define the rate of change. Addressing the amount of change that would be considered clinically significant will also be essential in planning clinical trials.