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Prodromal Markers of Upper Limb Deficits in FMR1 Premutation Carriers and Quantitative Outcome Measures for Future Clinical Trials in Fragile X‐associated Tremor/Ataxia Syndrome
Author(s) -
O'Keefe Joan A.,
Bang Deborah,
Robertson Erin E.,
Biskis Alexandras,
Ouyang Bichun,
Liu Yuanqing,
Pal Gian,
BerryKravis Elizabeth,
Hall Deborah A.
Publication year - 2020
Publication title -
movement disorders clinical practice
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.754
H-Index - 18
ISSN - 2330-1619
DOI - 10.1002/mdc3.13045
Subject(s) - ataxia , gait ataxia , intention tremor , rating scale , fmr1 , movement disorders , fragile x syndrome , postural tremor , physical medicine and rehabilitation , medicine , psychology , audiology , essential tremor , neuroscience , disease , psychiatry , fragile x , developmental psychology , biochemistry , chemistry , gene
Background Fragile X‐associated Tremor/Ataxia Syndrome (FXTAS) is a rare, late‐onset neurodegenerative disorder characterized by tremor and cerebellar gait ataxia, affecting premutation carriers (PMC) of CGG expansions (range, 55–200) in the fragile X mental retardation 1 ( FMR1 ) gene. Discovery of early predictors for FXTAS and quantitative characterization of motor deficits are critical for identifying disease onset, monitoring disease progression, and determining efficacy of interventions. Methods A total of 39 PMC with FXTAS, 20 PMC without FXTAS, and 27 healthy controls performed a series of upper extremity (UE) motor tasks assessing tremor, bradykinesia, and rapid alternating movements that were quantified using an inertial‐based sensor system (Kinesia One; Great Lakes NeuroTechnologies, Cleveland, OH, USA). Sub‐scores from the clinician‐rated FXTAS Rating Scale were correlated with the severity scores generated by the sensor system to determine its validity in FXTAS. Results PMC with FXTAS had significantly worse postural and kinetic tremor compared with PMC without FXTAS ( P = 0.02, 0.03) and controls ( P = 0.001, 0.0001), respectively, and slower finger tap ( P = 0.001), hand movement ( P = 0.0001), and rapid alternating movement speed ( P = 0.003) and amplitude ( P = 0.04) than controls. PMC without FXTAS had significantly worse right finger tap ( P = 0.004), hand movement ( P = 0.01), and rapid alternating movement speed ( P = 0.003) and amplitude ( P = 0.02) than controls. FXTAS Rating Scale subscores significantly correlated with all tremorography scores except for finger taps and left rapid alternating movement. Conclusions These findings support the use of inertial sensor quantification systems as promising measures for preclinical FXTAS symptom detection in PMC, characterization of the natural history of FXTAS, assessment of medication responses, and outcome assessment in clinical trials.