D'Cruz Nicholas, Vervoort Griet, Fieuws Steffen, Moreau Caroline, Vandenberghe Wim, Nieuwboer Alice
KU Leuven, Department of Rehabilitation Sciences, Neurorehabilitation Research Group, Leuven, Belgium.
KU Leuven, Leuven Biostatistics and Statistical Bioinformatics Centre (L-BioStat), Leuven, Belgium.
J Parkinsons Dis. 2020;10(2):559-571. doi: 10.3233/JPD-191759.
The onset of freezing of gait (FOG) represents a turning point in the lives of patients with Parkinson's disease (PD). FOG increases fall risk and is associated with worse physical and mental health related quality of life, thus increasing disease burden. Moreover, therapeutic studies aiming to ameliorate freezing have had limited success. In a step towards pre-emptive therapy to delay or prevent the onset of FOG, this prospective cohort study set out to uncover clinical markers of conversion to FOG.
Investigate clinical markers of conversion to FOG.
Sixty PD patients without FOG were followed up for two years and underwent extensive clinical testing each year. FOG classification was made with the New Freezing of Gait Questionnaire. Clinical predictors of conversion to FOG were investigated using univariate analysis and through building a multivariable model using all measured components.
Twelve patients developed FOG during the study (Incidence: 11.5% per year). Due to the large number of predictors, univariate analyses did not survive multiple comparison correction, precluding strong inference on any one predictor. Overall, the effect sizes suggested that motor deficits including difficulties with repetitive movement scaling (AUC: 0.71), coordination (AUC: 0.73) and consistency (AUC: 0.76) as well as gait asymmetry (AUC: 0.79) and variability (AUC: 0.71) were most predictive of conversion. Further, converters reported more subjective cognitive difficulty (AUC: 0.74), although their measured performance was similar to non-converters. Multivariable analyses further showed that the two components most consistently selected in the predictive model were: 1) an MDS-UPDRS component with worse axial motor, hand use and non-motor symptoms; and 2) finger tapping abnormalities.
Conversion to FOG was predicted mainly by objective and clinical measures of motor dyscontrol, as non-motor disturbances were surfacing. Although based on a small cohort with limited converters, this novel finding informs future studies aimed at FOG prevention.
冻结步态（FOG）的出现是帕金森病（PD）患者生活中的一个转折点。FOG增加了跌倒风险，并与身心健康相关生活质量较差有关，从而增加了疾病负担。此外，旨在改善冻结症状的治疗研究取得的成功有限。为了朝着延迟或预防FOG发作的预防性治疗迈出一步，这项前瞻性队列研究旨在揭示转变为FOG的临床标志物。
研究转变为FOG的临床标志物。
对60例无FOG的PD患者进行了两年的随访，每年进行广泛的临床测试。使用新的冻结步态问卷进行FOG分类。通过单变量分析并构建使用所有测量成分的多变量模型，研究转变为FOG的临床预测因素。
12例患者在研究期间出现了FOG（发病率：每年11.5%）。由于预测因素数量众多，单变量分析未能通过多重比较校正，无法对任何一个预测因素进行有力推断。总体而言，效应大小表明，包括重复运动缩放困难（AUC：0.71）、协调性（AUC：0.73）和一致性（AUC：0.76）以及步态不对称（AUC：0.79）和变异性（AUC：0.71）在内的运动缺陷最能预测转变。此外，转变者报告了更多主观认知困难（AUC：0.74），尽管他们的测量表现与未转变者相似。多变量分析进一步表明，预测模型中最一致选择的两个成分是：1）MDS-UPDRS中轴性运动、手部使用和非运动症状较差的一个成分；2）手指敲击异常。
转变为FOG主要由运动控制不良的客观和临床指标预测，因为非运动障碍正在显现。尽管基于一个转变者有限的小队列，但这一新颖发现为未来旨在预防FOG的研究提供了信息。
