摘要：

目的: 探讨初诊未服药帕金森病患者冻结步态（FOG）发生率、临床特征及影像学机制，并筛查帕金森病患者发生冻结步态的危险因素。方法: 回顾性纳入2018年10月至2024年9月在南京医科大学附属脑科医院就诊的初诊未服药帕金森病患者共250例，根据统一帕金森病评价量表第二部分（UPDRSⅡ）第14项评分分为FOG组（评分≥ 1分，45例）和nFOG组（评分为零，205例），并纳入性别、年龄和受教育程度相匹配的正常对照者55例。采用蒙特利尔认知评价量表（MoCA）评估所有受试者整体认知功能，汉密尔顿抑郁量表（HAMD）评估抑郁症状严重程度，汉密尔顿焦虑量表（HAMA）评估焦虑症状严重程度；采用UPDRSⅡ量表评估帕金森病患者日常生活活动能力，统一帕金森病评价量表第三部分（UPDRSⅢ）评估核心运动功能损害程度，改良Hoehn-Yahr分期评估病情严重程度及病程进展阶段，非运动症状问卷（NMSQ）评估非运动症状发生情况及症状负担。收集T₁WI结构像和静息态fMRI数据，提取灰质体积进行分析；通过低频振幅算法对脑自发活动水平进行分析。采用单因素和多因素逐步法Logistic回归分析筛查帕金森病患者发生冻结步态的危险因素。结果: 初诊未服药帕金森病患者冻结步态发生率为18%（45/250）。对照组、nFOG组与FOG组灰质体积比较差异无统计学意义（均校正P > 0.05）。3组间右侧顶下小叶标准化低频振幅（zALFF）值（F=14.961，P=0.000）、右侧距状回zALFF值（F=14.539，P=0.000）差异具有统计学意义，进一步两两比较，与对照组相比，nFOG组右侧距状回zALFF值降低（t=5.305，校正P=0.000），FOG组右侧顶下小叶zALFF值升高（t=-5.029，校正P=0.000），右侧距状回zALFF值降低（t=3.946，校正P=0.000）；与nFOG组相比，FOG组右侧顶下小叶zALFF值升高（t=-4.974，校正P=0.000）。Logistic回归分析显示，UPDRSⅡ评分高（OR=1.365，95%CI：1.227 ~ 1.518；P=0.000）和右侧顶下小叶zALFF值高（OR=5.021，95%CI：2.116 ~ 11.915；P=0.000）是帕金森病患者发生冻结步态的危险因素。结论: 早期帕金森病患者也可发生冻结步态，UPDRSⅡ评分高和右侧顶下小叶zALFF值异常增高是早期帕金森病患者发生冻结步态的危险因素。

关键词: 帕金森病, 步态障碍，神经性, 神经心理学测验, 磁共振成像, 危险因素, Logistic模型

Abstract:

Objective: To investigate the prevalence, clinical characteristics and neuroimaging mechanisms of freezing of gait (FOG) in de novo drug-naive patients with Parkinson's disease (PD), and to identify the risk factors for FOG in these patients. Methods: A total of 250 de novo drug-naive PD patients treated at The Affiliated Brain Hospital of Nanjing Medical University from October 2018 to September 2024 were retrospectively enrolled. According to item 14 score of Unified Parkinson's Disease Rating Scale Ⅱ (UPDRS Ⅱ), the PD patients were divided into the FOG group (score ≥ 1, n=45) and the non-FOG (nFOG) group (score=0, n=205). In addition, 55 gender, age and education matched healthy volunteers were included as healthy controls. The global cognitive function of all subjects was assessed using the Montreal Cognitive Assessment (MoCA), the severity of depressive symptoms was evaluated with the Hamilton Depression Rating Scale (HAMD), and the severity of anxiety symptoms was measured by the Hamilton Anxiety Rating Scale (HAMA). For PD patients, the activities of daily living were assessed using UPDRS Ⅱ, the severity of core motor impairment was evaluated with Unified Parkinson's Disease Rating Scale Ⅲ (UPDRS Ⅲ), the disease stage and progression were assessed using the modified Hoehn-Yahr stage, and non-motor symptoms and their burden were evaluated using the Non-Motor Symptoms Questionnaire (NMSQ). T₁WI and resting-state fMRI data were acquired, and the gray matter volume was extracted for analysis. The spontaneous brain activity levels were analyzed using the amplitude of low-frequency fluctuation (ALFF) algorithm. Univariate and multivariate stepwise Logistic regression analyses were performed to identify the risk factors for FOG in PD patients. Results: The prevalence of FOG in de novo drug-naive PD patients was 18% (45/250). No statistically significant differences in gray matter volume were found among the control group, FOG group and nFOG group (adjusted P > 0.05, for all). Statistically significant differences were detected in Z-score normalized amplitude of low-frequency fluctuation (zALFF) values of the right inferior parietal lobule (F=14.961, P=0.000) and right calcarine gyrus (F=14.539, P=0.000) among the 3 groups. Further pairwise comparisons showed that compared with the control group, the nFOG group exhibited decreased zALFF value in the right calcarine gyrus (t=5.305, adjusted P=0.000), the FOG group presented increased zALFF value in the right inferior parietal lobule (t=- 5.029, adjusted P=0.000) and decreased zALFF value in the right calcarine gyrus (t=3.946, adjusted P=0.000); while compared with the nFOG group, the FOG group had a higher zALFF value in the right inferior parietal lobule (t=- 4.974, adjusted P= 0.000). Logistic regression analysis showed that a higher UPDRS Ⅱ score (OR= 1.365, 95%CI: 1.227-1.518; P= 0.000) and zALFF value in the right inferior parietal lobule (OR=5.021, 95%CI: 2.116-11.915; P=0.000) were risk factors for FOG in PD patients. Conclusions: FOG can also occur in patients with early-stage PD. A high UPDRSⅡ score and abnormally increased zALFF value in the right inferior parietal lobule are risk factors for FOG in early-stage PD patients.

Key words: Parkinson disease, Gait disorders, neurologic, Neuropsychological tests, Magnetic resonance imaging, Risk factors, Logistic models

中图分类号: 

• R742.5