Early-onset drug-induced parkinsonism after exposure to offenders implies nigrostriatal dopaminergic dysfunction

J Neurol Neurosurg Psychiatry. 2018 Feb;89(2):169-174. doi: 10.1136/jnnp-2017-315873. Epub 2017 Sep 14.

Abstract

Objectives: The onset of parkinsonism in patients with drug-induced parkinsonism (DIP) exhibits extensive individual variability following exposure to offending drugs. We investigated whether the individual variations in the onset time of parkinsonism reflected the underlying subtle dopaminergic dysfunction in DIP.

Methods: We enrolled 71 patients with DIP who had visually normal striatal dopamine transporter (DAT) availability in 18F-FP-CIT positron emission tomography scans. According to their exposure durations to the offending drugs prior to onset of the parkinsonism, the patients were divided into the early-onset group (duration ≤6 months; n=35) and delayed-onset group (duration >6 months; n=36). We performed the quantitative analysis of the DAT availability in each striatal subregion between the groups.

Results: No patients with DIP had DAT availability that was more than 2 SD below the normal mean of DAT availability. Compared with the delayed-onset group, the early-onset DIP group had decreased DAT availability in the striatal subregions including the posterior putamen (p=0.018), anterior putamen (p=0.011), caudate (p=0.035) and ventral striatum (p=0.027). After adjusting for age, sex and cross-cultural smell identification test scores, a multivariate analysis revealed that the DAT availability in the striatal subregions of the patients with DIP was significantly and positively associated with the natural logarithm of the duration of drug exposure.

Conclusions: These results suggest that a short exposure to the offending drugs before the development of parkinsonism would be associated with subtle nigrostriatal dopaminergic dysfunction in patients with DIP.

Keywords: Parkinson’s disease; dopamine transporter; drug-induced parkinsonism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Anticonvulsants / adverse effects
  • Antiemetics / adverse effects
  • Antipsychotic Agents / adverse effects
  • Calcium Channel Blockers / adverse effects
  • Case-Control Studies
  • Caudate Nucleus / diagnostic imaging
  • Caudate Nucleus / metabolism
  • Corpus Striatum / diagnostic imaging
  • Corpus Striatum / metabolism*
  • Deprescriptions
  • Dopamine Plasma Membrane Transport Proteins / metabolism*
  • Female
  • Fluorine Radioisotopes
  • Humans
  • Male
  • Middle Aged
  • Neostriatum / diagnostic imaging
  • Neostriatum / metabolism
  • Parkinsonian Disorders / chemically induced
  • Parkinsonian Disorders / diagnostic imaging
  • Parkinsonian Disorders / metabolism*
  • Parkinsonian Disorders / physiopathology
  • Positron-Emission Tomography
  • Putamen / diagnostic imaging
  • Putamen / metabolism
  • Radiopharmaceuticals
  • Recovery of Function
  • Selective Serotonin Reuptake Inhibitors / adverse effects
  • Time Factors
  • Tropanes
  • Valproic Acid / adverse effects
  • Ventral Striatum / diagnostic imaging
  • Ventral Striatum / metabolism

Substances

  • Anticonvulsants
  • Antiemetics
  • Antipsychotic Agents
  • Calcium Channel Blockers
  • Dopamine Plasma Membrane Transport Proteins
  • Fluorine Radioisotopes
  • Radiopharmaceuticals
  • Serotonin Uptake Inhibitors
  • Tropanes
  • 2-carbomethoxy-8-(3-fluoropropyl)-3-(4-iodophenyl)tropane
  • Valproic Acid