Department of Biostatistics, University of Arkansas for Medical Sciences, Little Rock, AR, United States of America.
Department of Neurology, University of Arkansas for Medical Sciences, Little Rock, AR, United States of America.
PLoS One. 2022 Jun 2;17(6):e0269227. doi: 10.1371/journal.pone.0269227. eCollection 2022.
Freezing in the levodopa-medicated-state (ON-state) is a debilitating feature of Parkinson's disease without treatment options. Studies detailing the distinguishing features between people with freezing of gait that improves with levodopa and those whose freezing continues even on levodopa are lacking.
To characterize the gross motor, gait, and non-motor features of this phenotype.
Instrumented continuous gait was collected in the levodopa-medicated-state in 105 patients: 43 non-freezers (no-FOG), 36 with freezing only OFF-levodopa (OFF-FOG) and 26 with freezing both ON- and OFF-levodopa (ONOFF-FOG). Evaluation of motor and non-motor disease features was undertaken using validated scales. A linear mixed model with age, sex, disease duration, and motor UPDRS scores as covariates was used to determine differences in spatiotemporal gait and non-motor disease features among the groups.
Compared to OFF-FOG, the ONOFF-FOG group had greater disease severity (on the Unified Parkinson's disease Rating Scale) and worse cognition (on the Montreal Cognitive Assessment, Frontal Assessment Battery and Scales for Outcome in Parkinson's disease-Cognition scales) and quality of life (on the PDQ-39), but similar mood (on the Hamilton depression and anxiety scales) and sleep quality (on Epworth sleepiness scale and RBD questionnaire). For several gait features, differences between the ONOFF-OFF groups were at least as large and in the opposite direction as differences between OFF-no groups, controlling for disease severity. Variability in ONOFF-FOG was greater than in other groups. Using results from our study and others, a power analysis for a potential future study reveals sample sizes of at least 80 ONOFF and 80 OFF-FOG patients would be needed to detect clinically meaningful differences.
Intra-patient variability in spatiotemporal gait features was much greater in ONOFF-FOG than in the other two groups. Our results suggest that multifactorial deficits may lead to ONOFF-FOG development.
在左旋多巴治疗状态下（ON 状态）冻结是帕金森病的一种衰弱特征，目前尚无治疗方法。缺乏详细描述左旋多巴改善冻结步态与即使服用左旋多巴仍持续冻结步态患者之间区别的研究。
描述这种表型的总体运动、步态和非运动特征。
在 105 名患者的左旋多巴治疗状态下收集了仪器化连续步态：43 名非冻结者（无冻结步态，no-FOG）、36 名仅在停用左旋多巴时冻结者（OFF-FOG）和 26 名在 ON 和 OFF 时均冻结者（ONOFF-FOG）。使用经过验证的量表评估运动和非运动疾病特征。使用线性混合模型，以年龄、性别、疾病持续时间和运动 UPDRS 评分为协变量，确定各组之间时空步态和非运动疾病特征的差异。
与 OFF-FOG 相比，ONOFF-FOG 组疾病严重程度更高（在统一帕金森病评定量表上），认知功能更差（在蒙特利尔认知评估、额叶评估量表和帕金森病结局量表-认知量表上），生活质量更差（在帕金森病生活质量问卷-39 上），但情绪相似（在汉密尔顿抑郁和焦虑量表上），睡眠质量相似（在 Epworth 嗜睡量表和 RBD 问卷上）。对于几个步态特征，在控制疾病严重程度的情况下，ONOFF-FOG 组之间的差异至少与 OFF-no 组之间的差异一样大，方向相反。ONOFF-FOG 组的变异性大于其他组。使用我们研究和其他研究的结果，对未来潜在研究的功效分析表明，需要至少 80 名 ONOFF 和 80 名 OFF-FOG 患者的样本量才能检测到有临床意义的差异。
ONOFF-FOG 患者的时空步态特征的个体内变异性明显大于其他两组。我们的结果表明，多因素缺陷可能导致 ONOFF-FOG 的发展。
