Jansen Jamie A F, Capato Tamine T C, Darweesh Sirwan K L, Barbosa Egberto R, Donders Rogier, Bloem Bastiaan R, Nonnekes Jorik
Radboud University Medical Center, Donders Institute for Brain, Cognition and Behavior, Department of Rehabilitation, Center of Expertise for Parkinson & Movement Disorders, Nijmegen, The Netherlands.
University of São Paulo, Department of Neurology, Movement Disorders Center, São Paulo, Brazil.
NPJ Parkinsons Dis. 2023 Sep 9;9(1):130. doi: 10.1038/s41531-023-00575-0.
The relationship between dopaminergic treatment and freezing of gait (FOG) in Parkinson's disease (PD) is complex: levodopa is the most effective symptomatic treatment for FOG, but long-term pulsatile levodopa treatment has also been linked to an increase in the occurrence of FOG. This concept, however, continues to be debated. Here, we compared the occurrence of FOG between a levodopa-naive PD cohort and a levodopa-treated cohort. Forty-nine treatment-naive patients and 150 levodopa-treated patients were included. The time since first motor symptoms was at least 5 years. Disease severity was assessed using the MDS-UPDRS part III. Occurrence of FOG was assessed subjectively (new freezing-of-gait-questionnaire) and objectively (rapid turns test and Timed Up-and-Go test). The presence of FOG was compared between the levodopa-treated and levodopa-naive groups using a chi-square test of homogeneity. We also performed a binomial Firth logistic regression with disease duration, disease severity, country of inclusion, location of measurement, and executive function as covariates. Subjective FOG was more common in the levodopa-treated cohort (n = 41, 27%) compared to the levodopa-naive cohort (n = 2, 4%, p < 0.001). The association between FOG and levodopa treatment remained after adjustment for covariates (OR = 6.04, 95%Cl [1.60, 33.44], p = 0.006). Objectively verified FOG was more common in the levodopa-treated cohort (n = 21, 14%) compared to the levodopa-naive cohort (n = 1, 2%, p = 0.02). We found an association between long-term pulsatile levodopa treatment and an increased occurrence of FOG. Future studies should further explore the role of nonphysiological stimulation of dopamine receptors in generating FOG, as a basis for possible prevention studies.
帕金森病（PD）中多巴胺能治疗与冻结步态（FOG）之间的关系较为复杂：左旋多巴是治疗FOG最有效的对症治疗药物，但长期脉冲式左旋多巴治疗也与FOG发生率增加有关。然而，这一概念仍存在争议。在此，我们比较了未服用左旋多巴的PD队列和服用左旋多巴的队列中FOG的发生率。纳入了49例未接受过治疗的患者和150例接受左旋多巴治疗的患者。首次出现运动症状的时间至少为5年。使用MDS-UPDRS第三部分评估疾病严重程度。通过主观（新的冻结步态问卷）和客观（快速转身试验和定时起立行走试验）评估FOG的发生率。使用卡方同质性检验比较服用左旋多巴组和未服用左旋多巴组中FOG的存在情况。我们还进行了二项式Firth逻辑回归分析，将疾病持续时间、疾病严重程度、纳入国家、测量地点和执行功能作为协变量。与未服用左旋多巴的队列（n = 2，4%）相比，主观FOG在服用左旋多巴的队列中更为常见（n = 41，27%，p < 0.001）。在对协变量进行调整后，FOG与左旋多巴治疗之间的关联仍然存在（OR = 6.04，95%CI [1.60，33.44]，p = 0.006）。与未服用左旋多巴的队列（n = 1，2%）相比，经客观证实的FOG在服用左旋多巴的队列中更为常见（n = 21，14%，p = 0.02）。我们发现长期脉冲式左旋多巴治疗与FOG发生率增加之间存在关联。未来的研究应进一步探索多巴胺受体的非生理性刺激在产生FOG中的作用，作为可能的预防研究的基础。
