O'Keefe Joan A, Bang Deborah, Robertson Erin E, Biskis Alexandras, Ouyang Bichun, Liu Yuanqing, Pal Gian, Berry-Kravis Elizabeth, Hall Deborah A
Department of Cell & Molecular Medicine Rush University Medical Center Chicago Illinois USA.
Department of Neurological Sciences Rush University Medical Center Chicago Illinois USA.
Mov Disord Clin Pract. 2020 Aug 29;7(7):810-819. doi: 10.1002/mdc3.13045. eCollection 2020 Oct.
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 () 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.
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.
PMC with FXTAS had significantly worse postural and kinetic tremor compared with PMC without FXTAS ( = 0.02, 0.03) and controls ( = 0.001, 0.0001), respectively, and slower finger tap ( = 0.001), hand movement ( = 0.0001), and rapid alternating movement speed ( = 0.003) and amplitude ( = 0.04) than controls. PMC without FXTAS had significantly worse right finger tap ( = 0.004), hand movement ( = 0.01), and rapid alternating movement speed ( = 0.003) and amplitude ( = 0.02) than controls. FXTAS Rating Scale subscores significantly correlated with all tremorography scores except for finger taps and left rapid alternating movement.
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.
脆性X相关震颤/共济失调综合征（FXTAS）是一种罕见的迟发性神经退行性疾病，其特征为震颤和小脑性步态共济失调，影响脆性X智力低下1（FMR1）基因中CGG重复序列（范围为55 - 200）的前突变携带者（PMC）。发现FXTAS的早期预测指标并对运动缺陷进行定量表征对于确定疾病发作、监测疾病进展以及评估干预效果至关重要。
共有39名患有FXTAS的PMC、20名未患FXTAS的PMC以及27名健康对照者进行了一系列上肢（UE）运动任务，以评估震颤、运动迟缓以及快速交替运动，这些任务使用基于惯性的传感器系统（Kinesia One；美国俄亥俄州克利夫兰市的大湖神经技术公司）进行量化。临床医生评定的FXTAS评定量表的子分数与传感器系统生成的严重程度分数进行相关性分析，以确定其在FXTAS中的有效性。
与未患FXTAS的PMC（P = 0.02，0.03）和对照组（P = 0.001，0.0001）相比，患有FXTAS的PMC分别具有明显更严重的姿势性和运动性震颤，并且与对照组相比，其手指敲击速度（P = 0.001）、手部运动速度（P = 0.0001）以及快速交替运动速度（P = 0.003）和幅度（P = 0.04）更慢。未患FXTAS的PMC与对照组相比，其右手手指敲击速度（P = 0.004）、手部运动速度（P = 0.01）以及快速交替运动速度（P = 0.003）和幅度（P = 0.02）明显更慢。FXTAS评定量表子分数与除手指敲击和左侧快速交替运动外的所有震颤描记术分数均显著相关。
这些发现支持将惯性传感器量化系统作为在PMC中进行临床前FXTAS症状检测、表征FXTAS自然病史、评估药物反应以及在临床试验中进行结果评估的有前景的措施。
