Molparia Bhuvan, Schrader Brian N, Cohen Eli, Wagner Jennifer L, Gupta Sandeep R, Gould Sherrie, Hwynn Nelson, Spencer Emily G, Torkamani Ali
The Scripps Translational Science Institute, The Scripps Research Institute, La Jolla, CA, USA.
Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA, USA.
PeerJ. 2018 Jul 20;6:e5308. doi: 10.7717/peerj.5308. eCollection 2018.
Essential tremor (ET) and Parkinson's disease (PD) are among the most common adult-onset tremor disorders. Clinical and pathological studies suggest that misdiagnosis of PD for ET, and vice versa, occur in anywhere from 15% to 35% of cases. Complex diagnostic procedures, such as dopamine transporter imaging, can be powerful diagnostic aids but are lengthy and expensive procedures that are not widely available. Preliminary studies suggest that monitoring of tremor characteristics with consumer grade accelerometer devices could be a more accessible approach to the discrimination of PD from ET, but these studies have been performed in well-controlled clinical settings requiring multiple maneuvers and oversight from clinical or research staff, and thus may not be representative of at-home monitoring in the community setting. Therefore, we set out to determine whether discrimination of PD vs. ET diagnosis could be achieved by monitoring research subject movements at home using consumer grade devices, and whether discrimination could be improved with the addition of genetic profiling of the type that is readily available through direct-to-consumer genetic testing services. Forty subjects with PD and 27 patients with ET were genetically profiled and had their movements characterized three-times a day for two weeks through a simple procedure meant to induce rest tremors. We found that tremor characteristics could be used to predict diagnosis status (sensitivity = 76%, specificity = 65%, area under the curve (AUC) = 0.75), but that the addition of genetic risk information, via a PD polygenic risk score, did not improve discriminatory power (sensitivity = 80%, specificity = 65%, AUC = 0.73).
特发性震颤(ET)和帕金森病(PD)是最常见的成人起病的震颤疾病。临床和病理学研究表明,PD误诊为ET以及ET误诊为PD的情况在15%至35%的病例中都有发生。复杂的诊断程序,如多巴胺转运体成像,可能是强大的诊断辅助手段,但这些程序冗长且昂贵,并非广泛可用。初步研究表明,使用消费级加速度计设备监测震颤特征可能是一种更易于区分PD和ET的方法,但这些研究是在严格控制的临床环境中进行的,需要多次操作并由临床或研究人员监督,因此可能无法代表社区环境中的家庭监测情况。因此,我们着手确定是否可以通过使用消费级设备在家中监测研究对象的运动来实现PD与ET诊断的区分,以及通过添加可通过直接面向消费者的基因检测服务轻松获得的基因谱分析是否可以提高区分能力。40名PD患者和27名ET患者进行了基因谱分析,并通过一个旨在诱发静息震颤的简单程序,在两周内每天三次对他们的运动进行特征描述。我们发现震颤特征可用于预测诊断状态(敏感性 = 76%,特异性 = 65%,曲线下面积(AUC) = 0.75),但通过PD多基因风险评分添加基因风险信息并不能提高区分能力(敏感性 = 80%,特异性 = 65%,AUC = 0.73)。