Nürnberger Lucas, Klein Christine, Baudrexel Simon, Roggendorf Julia, Hildner Marcel, Chen Shu, Kang Jun-Suk, Hilker Rüdiger, Hagenah Johann
Department of Neurology, University of Frankfurt am Main, Germany.
Mov Disord. 2015 Mar;30(3):386-92. doi: 10.1002/mds.26127. Epub 2014 Dec 27.
Carriers of a single heterozygous PINK1 (PTEN-induced putative kinase 1) gene mutation provide an ideal opportunity to study the development of parkinsonian motor signs from the very beginning. Measuring tools that reliably represent mild motor symptoms could also facilitate the assessment of future neuroprotective therapies and early diagnosis of Parkinson's disease (PD). We investigated nine family members carrying a heterozygous PINK1 mutation in comparison with 25 age-matched healthy controls. Arm kinematics were quantified during treadmill walking at four different speeds using ultrasound-based motion analysis. Heterozygous PINK1 mutation carriers showed a bilateral reduction of arm swing amplitudes (P = 0.003) and arm anteversion (P = 0.001), which was more pronounced on the predominantly affected body side but also was present, albeit to a lesser degree, contralaterally (amplitude P = 0.01, anteversion P = 0.002, repeated measures analysis of covariance [rmANCOVA]). Single post-hoc comparisons revealed similar results for all speeds on both body sides (P < 0.05) except for 2.0 km/h on the less affected side. A single heterozygous mutation in the PINK1 gene is associated with a bilateral dopaminergic dysfunction in this family. Ultrasound-based three-dimensional motion analysis of arm swing during gait is a suitable tool to quantify even subtle hypokinesia in mildly affected PINK1 mutation carriers, which tends to be easily overlooked on the less affected body side during clinical examination. Therefore, this technique is a promising application in early stage PD and in at-risk populations for the disease.
携带单个杂合型PINK1（PTEN诱导的假定激酶1）基因突变的个体为从一开始就研究帕金森运动症状的发展提供了理想机会。能够可靠反映轻度运动症状的测量工具也有助于评估未来的神经保护疗法以及帕金森病（PD）的早期诊断。我们对9名携带杂合型PINK1突变的家庭成员与25名年龄匹配的健康对照者进行了研究。使用基于超声的运动分析，在跑步机以四种不同速度行走期间对手臂运动学进行了量化。杂合型PINK1突变携带者表现出双侧手臂摆动幅度降低（P = 0.003）和手臂前倾角降低（P = 0.001），在主要受影响的身体一侧更为明显，但对侧也存在，尽管程度较轻（幅度P = 0.01，前倾角P = 0.002，重复测量协方差分析[rmANCOVA]）。单因素事后比较显示，除了在受影响较小一侧的2.0 km/h速度外，身体两侧所有速度的结果均相似（P < 0.05）。在这个家族中，PINK1基因的单个杂合突变与双侧多巴胺能功能障碍有关。基于超声的步态期间手臂摆动三维运动分析是一种合适的工具，可用于量化轻度受影响的PINK1突变携带者中即使是细微的运动迟缓，在临床检查期间，这种运动迟缓在受影响较小的身体一侧往往容易被忽视。因此，这项技术在PD早期阶段和该疾病的高危人群中具有广阔的应用前景。
