Impaired Vestibular Control Mechanisms Underlie Balance Deficits in Fragile X-Associated Tremor/Ataxia Syndrome (P06.051)

Abstract

Objective: To characterize balance deficits in FXTAS via computerized dynamic posturography (CDP). Background Fragile X-associated tremor ataxia syndrome (FXTAS) is a movement disorder associated with premutation range expansions (55-200 CGG repeats) in the fragile X mental retardation 1 (FMR1) gene. Patients with FXTAS demonstrate kinetic tremor and cerebellar gait ataxia, associated with falls and ultimately disability. However, no studies have been performed to characterize the balance deficits in these patients or in premutation carriers not yet manifesting FXTAS symptoms. Design/Methods: We investigated balance using Neurocom ® Balance Master computerized dynamic posturography (CDP) in 17 FMR1 premutation carriers (FXTAS rating scale 5-52, normal Results: Patients 60-69 years old (y.o.) (n=8) and >70 y.o. (n=6) demonstrated significantly lower scores than HC on conditions 5 (p=.02; p =.04) and 6 (p=.001; p=.0008) of the SOT, signifying dysfunction of the vestibular system and/or its connections. Response latencies to medium and large forward and backward translations were significantly longer (p=.002 to 70 y.o. group. Similar trends were found in the Conclusions: FMR1 premutation carriers with FXTAS symptoms and some without symptoms on physical exam demonstrate balance deficits on CDP predominantly involving the vestibular system. In addition, their response latencies to balance perturbations are prolonged. FXTAS balance symptoms have been attributed primarily to cerebellar dysfunction, but our findings show that impaired cerebellar-vestibular connections play a key role. This information will be useful in designing preventative, rehabilitation, and medical treatments for FXTAS. Supported by: Partially funded by a Rush University Dean9s fellowship to EJ Dunn. Disclosure: Dr. Dunn has nothing to disclose. Dr. Hall has nothing to disclose. Dr. O9Keefe has nothing to disclose. Dr. Berry-Kravis has nothing to disclose. Dr. Ouyang has nothing to disclose.