title: Dyskinesia and the antiparkinsonian response always temporally coincide: a retrospective study.
abstract: OBJECTIVE
  To clinically characterize the temporal relationship between dyskinesia and the antiparkinsonian response when dyskinesia first emerges during long-term levodopa therapy and to determine if it is consistent with the hypothesized mechanism by which dyskinesia develops.
  
  
  METHODS
  Dyskinesia and the antiparkinsonian response to levodopa during 2-hour levodopa infusions were monitored at intervals through the first 4 years of long-term levodopa therapy in 20 subjects with idiopathic Parkinson disease (PD) and previously untreated with levodopa. The onset and offset of the antiparkinsonian response and dyskinesia were compared when dyskinesia first appeared during the 4 years. The findings were compared to 20 subjects with PD on long-term levodopa with dyskinesia and motor fluctuations.
  
  
  RESULTS
  The onset and offset of the antiparkinsonian response and dyskinesia generally coincided when dyskinesia first appeared during the 4 years and did not suggest any temporal dissociation of the 2 responses. Further, the latency to the onsets of dyskinesia and the antiparkinsonian response tended to shorten during long-term levodopa therapy, suggesting that both responses were sensitized by long-term levodopa.
  
  
  CONCLUSIONS
  The similar onsets and offsets of the antiparkinsonian response and dyskinesia when dyskinesia first appears are not consistent with the postulated progressive decrease in threshold for dyskinesia during long-term levodopa therapy. Other mechanisms for the development of dyskinesia need to be considered.
authors.affiliation: Department of Neurology, Oregon Health and Science University, Portland, OR 97239, USA. nuttj@ohsu.edu
authors.forename: John G
authors.initials: JG
authors.lastname: Nutt
authors.forename: Kathy A
authors.initials: KA
authors.lastname: Chung
authors.forename: Nicholas H G
authors.initials: NH
authors.lastname: Holford
mesh_terms: D000368:Aged; D000978:Antiparkinson Agents / Q000009:adverse effects; D018450:Disease Progression; D004409:Dyskinesia, Drug-Induced; D006801:Humans; D007980:Levodopa / Q000009:adverse effects*; D008875:Middle Aged; D010300:Parkinson Disease / Q000188:drug therapy*; D012189:Retrospective Studies; D012720:Severity of Illness Index; D013997:Time Factors
chemical_list: D000978:Antiparkinson Agents; D007980:Levodopa