Joan A O'Keefe1,2, Deborah Bang2, Erin E Robertson1, Alexandras Biskis1,3, Bichun Ouyang2, Yuanqing Liu2, Gian Pal2, Elizabeth Berry-Kravis2,4, Deborah A Hall2. 1. Department of Cell & Molecular Medicine Rush University Medical Center Chicago Illinois USA. 2. Department of Neurological Sciences Rush University Medical Center Chicago Illinois USA. 3. Department of Pediatrics Rush University Medical Center Chicago Illinois USA. 4. Department of Biochemistry Rush University Medical Center Chicago Illinois USA.
Abstract
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.
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.
Authors: Elizabeth Berry-Kravis; Liane Abrams; Sarah M Coffey; Deborah A Hall; Claudia Greco; Louise W Gane; Jim Grigsby; James A Bourgeois; Brenda Finucane; Sebastien Jacquemont; James A Brunberg; Lin Zhang; Janet Lin; Flora Tassone; Paul J Hagerman; Randi J Hagerman; Maureen A Leehey Journal: Mov Disord Date: 2007-10-31 Impact factor: 10.338
Authors: M A Leehey; E Berry-Kravis; C G Goetz; L Zhang; D A Hall; L Li; C D Rice; R Lara; J Cogswell; A Reynolds; L Gane; S Jacquemont; F Tassone; J Grigsby; R J Hagerman; P J Hagerman Journal: Neurology Date: 2007-12-05 Impact factor: 9.910
Authors: Deborah A Hall; Glenn T Stebbins; Sebastien Jacquemont; Elizabeth Berry-Kravis; Christopher G Goetz; Randi Hagerman; Lin Zhang; Maureen A Leehey Journal: Mov Disord Clin Pract Date: 2019-01-22
Authors: Padmaja Vittal; Shrikant Pandya; Kevin Sharp; Elizabeth Berry-Kravis; Lili Zhou; Bichun Ouyang; Jonathan Jackson; Deborah A Hall Journal: Neurol Genet Date: 2018-07-27
Authors: Jessica Klusek; Roger Newman-Norlund; Amanda J Fairchild; Sarah Newman-Norlund; Sara Sayers; Jill C Stewart; Elizabeth Berry-Kravis; Julius Fridriksson Journal: Arch Gerontol Geriatr Date: 2022-08-12 Impact factor: 4.163