From the Department of Neurology (H.Z., M.F.D., J.W.P., B.R.B., R.C.H.), Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Centre, Nijmegen, the Netherlands; and Departments of Neurology (H.Z.) and Emergency Medicine (D.R.), Medical University Vienna, Austria.
Neurology. 2020 Sep 15;95(11):e1461-e1470. doi: 10.1212/WNL.0000000000010316. Epub 2020 Jul 10.
We tested the hypothesis that there are 2 distinct phenotypes of Parkinson tremor, based on interindividual differences in the response of resting tremor to dopaminergic medication. We also investigated whether this pattern is specific to tremor by comparing interindividual differences in the dopamine response of tremor to that of bradykinesia.
In this exploratory study, we performed a levodopa challenge in 76 tremulous patients with Parkinson tremor. Clinical scores (Movement Disorders Society-sponsored version of the Unified Parkinson's Disease Rating Scale part III) were collected "off" and "on" a standardized dopaminergic challenge (200/50 mg dispersible levodopa-benserazide). In both sessions, resting tremor intensity was quantified using accelerometry, both during rest and during cognitive coactivation. Bradykinesia was quantified using a speeded keyboard test. We calculated the distribution of dopamine-responsiveness for resting tremor and bradykinesia. In 41 patients, a double-blinded, placebo-controlled dopaminergic challenge was repeated after approximately 6 months.
The dopamine response of resting tremor, but not bradykinesia, significantly departed from a normal distribution. A cluster analysis on 3 clinical and electrophysiologic markers of tremor dopamine-responsiveness revealed 3 clusters: dopamine-responsive, intermediate, and dopamine-resistant tremor. A repeated levodopa challenge after 6 months confirmed this classification. Patients with dopamine-responsive tremor had greater disease severity and tended to have a higher prevalence of dyskinesia.
Parkinson resting tremor can be divided into 3 partially overlapping phenotypes, based on the dopamine response. These tremor phenotypes may be associated with different underlying pathophysiologic mechanisms, requiring a different therapeutic approach.
我们基于个体间静止性震颤对多巴胺能药物反应的差异，检验帕金森震颤存在 2 种不同表型的假设。我们还通过比较震颤对多巴胺的反应与运动徐缓对多巴胺的反应，来研究这种模式是否是震颤特有的。
在这项探索性研究中，我们对 76 例震颤的帕金森病患者进行了左旋多巴挑战。临床评分（运动障碍协会赞助的帕金森病统一评定量表第三部分）在“关闭”和“开启”标准化多巴胺挑战（200/50mg 可分散左旋多巴-卡比多巴）时进行收集。在这两个阶段，使用加速度计在休息和认知共激活期间定量测量静止性震颤的强度。使用一个快速键盘测试来定量运动徐缓。我们计算了静止性震颤和运动徐缓的多巴胺反应分布。在 41 例患者中，大约 6 个月后，进行了双盲、安慰剂对照的多巴胺能挑战重复。
静止性震颤的多巴胺反应，但不是运动徐缓，明显偏离正态分布。对 3 项震颤多巴胺反应的临床和电生理标志物进行聚类分析，发现了 3 个簇：多巴胺反应性、中间和多巴胺抵抗性震颤。6 个月后的重复左旋多巴挑战证实了这种分类。多巴胺反应性震颤的患者疾病严重程度更高，且往往更易出现运动障碍。
基于多巴胺反应，帕金森静止性震颤可分为 3 种部分重叠的表型。这些震颤表型可能与不同的潜在病理生理机制有关，需要不同的治疗方法。
