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有症状和临床前亨廷顿舞蹈病患者的书写运动异常

Handwriting Movement Abnormalities in Symptomatic and Premanifest Huntington's Disease.

作者信息

Caligiuri Michael, Snell Chase, Park Sungmee, Corey-Bloom Jody

机构信息

Department of Psychiatry University of California San Diego La Jolla California USA.

Department of Neurosciences University of California San Diego La Jolla California USA.

出版信息

Mov Disord Clin Pract. 2019 Aug 16;6(7):586-592. doi: 10.1002/mdc3.12824. eCollection 2019 Sep.

Abstract

BACKGROUND

Kinematic measures of handwriting movements are sensitive to mild subclinical motor abnormalities stemming from a wide range of disorders involving the basal ganglia including Huntington's disease (HD). Prior research has not investigated handwriting movements in at-risk individuals in the premanifest stage of HD.

OBJECTIVES

The purpose of this study was to examine whether handwriting movement abnormalities are present prior to clinically manifest chorea in HD.

METHODS

A total of 38 symptomatic HD, 30 gene-positive premanifest, and 25 healthy control participants completed handwriting tasks consisting of circles, loops, sentences, and spirals with a noninking pen on a digitizing tablet. Multiple measures of pen stroke kinematics and pressure were measured along with the cognitive and motor status of each participant. Burden of pathology and CAG × age product scores were obtained from each participant with HD.

RESULTS

Participants with HD exhibited significantly longer and more variable stroke durations, decreased handwriting smoothness, and increased and more variable pen pressures when compared with the healthy controls. We found significant positive associations between stroke duration and both burden of pathology and CAG × age product. Results from a discriminant function analysis revealed a 7-factor model that distinguished premanifest from healthy controls with 85% accuracy. Factors in the model included greater variability in stroke amplitude, velocity and pen pressure, higher levels of pen pressure, longer stroke durations, and lower velocities for combinations of handwritten circles, sentences, and spirals.

CONCLUSIONS

These findings support the clinical utility of dynamic measures of handwriting kinematics as a potential early behavioral biomarker in HD.

摘要

背景

笔迹运动的运动学测量对源于包括亨廷顿舞蹈病(HD)在内的涉及基底神经节的多种疾病的轻度亚临床运动异常敏感。先前的研究尚未调查HD临床前期有患病风险个体的笔迹运动情况。

目的

本研究的目的是检查HD患者在临床上出现舞蹈症之前是否存在笔迹运动异常。

方法

共有38名有症状的HD患者、30名基因阳性的临床前期患者和25名健康对照参与者,使用非墨水笔在数位板上完成由画圈、画环、写句子和画螺旋线组成的笔迹任务。测量了笔的笔画运动学和压力的多项指标,以及每位参与者的认知和运动状态。从每位HD患者处获取病理负担和CAG×年龄乘积分数。

结果

与健康对照相比,HD患者表现出明显更长且更具变异性的笔画持续时间、笔迹流畅性降低,以及笔压力增加且更具变异性。我们发现笔画持续时间与病理负担和CAG×年龄乘积均呈显著正相关。判别函数分析的结果显示,一个7因素模型能够以85%的准确率区分临床前期患者和健康对照。该模型中的因素包括手写圆圈、句子和螺旋线组合时笔画幅度、速度和笔压力的更大变异性、更高的笔压力水平、更长的笔画持续时间以及更低的速度。

结论

这些发现支持了笔迹运动学动态测量作为HD潜在早期行为生物标志物的临床实用性。

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Micrographia in Huntington's disease.亨廷顿病中的显微绘图。
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