Dopamine-responsive and dopamine-resistant resting tremor in Parkinson disease

Neurology. 2020 Sep 15;95(11):e1461-e1470. doi: 10.1212/WNL.0000000000010316. Epub 2020 Jul 10.


Objective: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

Publication types

  • Controlled Clinical Trial

MeSH terms

  • Accelerometry
  • Adult
  • Aged
  • Aged, 80 and over
  • Antiparkinson Agents / therapeutic use*
  • Dopamine Agents / therapeutic use*
  • Double-Blind Method
  • Drug Resistance / drug effects*
  • Drug Resistance / physiology
  • Female
  • Follow-Up Studies
  • Humans
  • Hypokinesia / diagnostic imaging
  • Hypokinesia / drug therapy
  • Hypokinesia / physiopathology
  • Levodopa / therapeutic use*
  • Male
  • Middle Aged
  • Netherlands / epidemiology
  • Parkinson Disease / diagnostic imaging
  • Parkinson Disease / drug therapy*
  • Parkinson Disease / physiopathology
  • Treatment Outcome
  • Tremor / diagnostic imaging
  • Tremor / drug therapy*
  • Tremor / physiopathology


  • Antiparkinson Agents
  • Dopamine Agents
  • Levodopa