A Quantitative Assessment of Tremor and Ataxia in Female FMR1 Premutation Carriers Using CATSYS

Abstract

The fragile X-associated tremor/ataxia syndrome (FXTAS) is a relatively common cause of balance problems leading to gait disturbances in older males (40%) with the premutation. FXTAS is less common in females. We utilized the CATSYS system, a quantitative measure of movement, in 23 women with FXTAS (mean age 62.7; SD 12.3), 90 women with the premutation without FXTAS (mean age 52.9; SD 9.4), and 37 controls (mean age 56.53; SD 7.8). CATSYS distinguished differences between carriers with and without FXTAS in postural tremor, postural sway, hand coordination, and reaction time tasks. Differences were also seen between carriers without FXTAS and controls in finger tapping, reaction time, and one postural sway task. However, these differences did not persist after statistical correction for multiple comparisons. Notably, there were no differences across groups in intention tremor. This is likely due to the milder symptoms in females compared to males with FXTAS.

Figure 1

(a) Distribution/boxplots of (log) sway area (mm²) for eyes open 30 sec. task. Sway area was significantly higher in patients with FXTAS, compared to controls (P < .0001), as well as non-FXTAS (P < .0001). (Note: results unaffected by an outlying observation.) (Interior box horizontal bar = median). (b) Distribution/boxplots of (log) postural tremor intensity (m/sec²) in dominant hand (similar results for nondominant hand). Postural tremor intensity was significantly higher in patients with FXTAS, compared to controls (P < .0001), as well as non-FXTAS (P < .0001). (Note: results unaffected by outlying observations.) (Interior box horizontal bar = median).

Figure 2

(a) Proportion of variation explained by each principal component based on all 24 CATSYS measures, and adjusted for age. The first 3 principal components account for the majority total data variation (∼60%). (b) The 24 individual variables of the CATSYS and their correlation to the first 3 principal components. The first PC (PC1) summarizes predominantly all sway tasks; the second PC (PC2) is primarily correlated with intention tremor (DotTrem) and writing tremor (WritTrem) in both hands; the third PC (PC3) captures association with postural tremor (TremInt) and reaction time in both hands. S1: SwayO60_Mean, S2: SwayO60_Area, S3: SwayO60_Int, S4: SwayO30_Mean, S5: SwayO30_Area, S6: SwayO30_Int, S7: SwayC30_Mean, S8: SwayC30_Area, S9: SwayC30_Int, S10: SwayC10_Mean, S11: SwayC10_Area, S12: SwayC10_Int, T1: TremInt_Dom, T2: TremIntNon_Dom, D1: DotTremInt_Dom, D2: DotTremIntNon_Dom, W1: WritTremInt_Dom, W2: WritTremIntNon_Dom, M1: Maxfreq_Dom, M2: MaxfreqNon_Dom, M3: MaxfreqTap_Dom, M4: MaxfreqTapNon_Dom, R1: ReactAvg_Dom, R2: ReactAvgNon_Dom.