San Luciano Marta, Wang Cuiling, Ortega Roberto A, Yu Qiping, Boschung Sarah, Soto-Valencia Jeannie, Bressman Susan B, Lipton Richard B, Pullman Seth, Saunders-Pullman Rachel
Department of Neurology, Mount Sinai Beth Israel Medical Center, New York, New York, United States of America.
Department of Neurology, University of California San Francisco, San Francisco, California, United States of America.
PLoS One. 2016 Oct 12;11(10):e0162799. doi: 10.1371/journal.pone.0162799. eCollection 2016.
Pre-clinical markers of Parkinson's Disease (PD) are needed, and to be relevant in pre-clinical disease, they should be quantifiably abnormal in early disease as well. Handwriting is impaired early in PD and can be evaluated using computerized analysis of drawn spirals, capturing kinematic, dynamic, and spatial abnormalities and calculating indices that quantify motor performance and disability. Digitized spiral drawing correlates with motor scores and may be more sensitive in detecting early changes than subjective ratings. However, whether changes in spiral drawing are abnormal compared with controls and whether changes are detected in early PD are unknown.
138 PD subjects (50 with early PD) and 150 controls drew spirals on a digitizing tablet, generating x, y, z (pressure) data-coordinates and time. Derived indices corresponded to overall spiral execution (severity), shape and kinematic irregularity (second order smoothness, first order zero-crossing), tightness, mean speed and variability of spiral width. Linear mixed effect adjusted models comparing these indices and cross-validation were performed. Receiver operating characteristic analysis was applied to examine discriminative validity of combined indices.
All indices were significantly different between PD cases and controls, except for zero-crossing. A model using all indices had high discriminative validity (sensitivity = 0.86, specificity = 0.81). Discriminative validity was maintained in patients with early PD.
Spiral analysis accurately discriminates subjects with PD and early PD from controls supporting a role as a promising quantitative biomarker. Further assessment is needed to determine whether spiral changes are PD specific compared with other disorders and if present in pre-clinical PD.
帕金森病（PD）的临床前标志物是必要的，并且要在临床前疾病中具有相关性，它们在疾病早期也应该有可量化的异常。PD患者早期手部书写功能受损，可以通过对所画螺旋线进行计算机分析来评估，捕捉运动学、动力学和空间异常，并计算量化运动表现和残疾程度的指标。数字化螺旋线绘图与运动评分相关，并且在检测早期变化方面可能比主观评分更敏感。然而，与对照组相比，螺旋线绘图的变化是否异常以及在早期PD中是否能检测到变化尚不清楚。
138名PD患者（50名早期PD患者）和150名对照者在数字化平板电脑上绘制螺旋线，生成x、y、z（压力）数据坐标和时间。导出的指标对应于螺旋线的整体执行情况（严重程度）、形状和运动不规则性（二阶平滑度、一阶过零）、紧密程度、平均速度和螺旋线宽度的变异性。进行了比较这些指标的线性混合效应调整模型和交叉验证。应用受试者工作特征分析来检验组合指标的判别效度。
除过零指标外，PD病例组和对照组之间所有指标均有显著差异。使用所有指标的模型具有较高的判别效度（敏感性 = 0.86，特异性 = 0.81）。早期PD患者也保持了判别效度。
螺旋线分析能够准确地区分PD患者和早期PD患者与对照组，支持其作为一种有前景的定量生物标志物的作用。需要进一步评估以确定与其他疾病相比，螺旋线变化是否具有PD特异性，以及是否存在于临床前PD中。
