Impaired eye movements in presymptomatic spinocerebellar ataxia type 6
Impaired eye movements in presymptomatic spinocerebellar ataxia type 6
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DOI：
10.1001/archneur.65.4.530
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发表时间：
2008-04-01
影响因子：
--
通讯作者：
Gomez, Christopher M.
中科院分区：
文献类型：
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作者：
Christova, Peka;Anderson, John H.;Gomez, Christopher M.
背景资料：神经退行性疾病中神经功能受损的早期检测可能有助于了解疾病的发病机制和治疗试验的时机。目的：确定具有脊髓小脑共济失调6型（SCA 6）基因（CACNA 1A）但无临床症状的个体的眼运动功能的早期异常。设计：使用生理技术记录和分析眼球运动和姿势摇摆。患者：结果：症状前患者有正常的姿势摆动，但明确的眼运动异常。2例出现低振幅水平凝视诱发的眼球震颤，其中1例向上扫视的眼速显著降低，方波抽搐频率异常。另一个有不正常的方波抖动，第四个有一个减少的增益追求跟踪。不是所有的前驱患者有相同的结果，但多变量分析歧视前驱患者，作为一个组，从健康对照组和共济失调patients.Conclusions：在SCA 6最早的功能缺陷是眼动异常，包括受损的扫视速度，扫视指标，追求增益。这表明早期功能障碍是由小脑后蚓部和小叶的细胞功能障碍和/或丧失引起的。这些发现可能有助于确定治疗的时机，并定义可用作治疗试验疗效的结局指标的变量。
Background: Early detection of impaired neurological function in neurodegenerative diseases may aid in understanding disease pathogenesis and timing of therapeutic trials.Objective: To identify early abnormalities of ocular motor function in individuals who have the spinocerebellar ataxia type 6 (SCA6) gene (CACNA1A) but no clinical symptoms.Design: Physiological techniques were used to record and analyze eye movements and postural sway.Patients: Four presymptomatic and 5 ataxic patients with SCA6, genetically identified, and 10 healthy controls.Results: Presymptomatic individuals had normal postural sway but definite ocular motor abnormalities. Two had a low-amplitude horizontal gaze-evoked nystagmus, 1 of whom had a significantly decreased eye velocity for upward saccades and an abnormal frequency of square-wave jerks. Another had abnormal square-wave jerks and a fourth had a reduced gain for pursuit tracking. Not all of the presymptomatic patients had the same findings, but a multivariate analysis discriminated the presymptomatic patients, as a group, from healthy controls and the ataxic patients.Conclusions: Among the earliest functional deficits in SCA6 are eye movement abnormalities, including impaired saccade velocity, saccade metrics, and pursuit gain. This suggests that early functional impairments are caused by cellular dysfunction and/or loss in the posterior cerebellar vermis and flocculus. These findings might help to determine the timing of a treatment and to define variables that could be used as outcome measures for the efficacy of therapeutic trials.