Objective: To conduct gait and balance “stress” tests including those with dual task (DT) cognitive interference which we hypothesized would reveal early motor impairments in asymptomatic fragile X mental retardation 1 (FMR1) premutation (PM) carriers.

Background: Carriers of a premutation size 55-200 CGG repeat expansion in the FMR1 gene are at risk for developing FXTAS, a neurodegenerative disorder marked by cerebellar ataxia, balance deficits, and cognitive impairment.  Risk factors for developing FXTAS are not completely understood and early preclinical detection methods are needed. 

Methods: PM carriers without FXTAS (n=14; 62.4 ± 9.4 yrs), PM carriers with FXTAS (n=9; 67.1 ± 10.1 yrs) and healthy controls (n=22; 60.0 + 10.8 yrs) underwent gait and balance testing.  Quantitative assessment of gait and turning via a 2 minute walk test and postural control (i-SWAY) were performed utilizing an inertial sensor system (APDM; Oregon).  Gait analysis was performed during a self-selected and fast as possible pace and a DT condition.  Stance (feet apart/together), vision (eyes open/closed), surface stability (firm/foam surface), and cognitive demand (single task/DT) were altered to modulate the postural challenge on the i-SWAY.  DT conditions for balance and gait consisted of a simultaneous verbal fluency task. 

Results: PM carriers with and without FXTAS exhibited worse balance on the i-SWAY than controls, with more difficult conditions (feet together/eyes closed/foam) yielding the most highly significant results (p = 0.04 to < 0.0001).  During fast paced gait, carriers without FXTAS demonstrated significantly reduced total distance traveled (p = 0.03), reduced cadence (p = 0.04), and longer turn step time (p = 0.046).  They also had significantly slower stride velocities during DT walking (p < 0.0001) and their DT cost for total distance walked was higher than controls (p < 0.05).

Conclusions: PM carriers without FXTAS demonstrate worse gait performance at fast paced speeds and under DT conditions and worse balance under environmentally challenging conditions.  This suggests that such balance and gait tests using state of the art quantitative measures may be sensitive to produce at risk markers for FXTAS.  Identification of preclinical signs of motor impairments in FXTAS will potentially establish an early intervention window for providing preventative rehabilitation strategies and disease modifying drugs.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/potential-preclinical-gait-and-balance-markers-for-developing-fragile-x-associated-tremorataxia-syndrome-fxtas/