Graft-induced dyskinesias in Parkinson's disease: High striatal serotonin/dopamine transporter ratio

Mov Disord. 2011 Sep;26(11):1997-2003. doi: 10.1002/mds.23743. Epub 2011 May 24.

Abstract

Graft-induced dyskinesias are a serious complication after neural transplantation in Parkinson's disease. One patient with Parkinson's disease, treated with fetal grafts 14 years ago and deep brain stimulation 6 years ago, showed marked improvement of motor symptoms but continued to suffer from OFF-medication graft-induced dyskinesias. The patient received a series of clinical and imaging assessments. Positron emission tomography and single-photon emission computed tomography 14 years posttransplantation revealed an elevated serotonin/dopamine transporter ratio in the grafted striatum compatible with serotonergic hyperinnervation. Inhibition of serotonin neuron activity by systemic administration of a 5-HT(1A) agonist suppressed graft-induced dyskinesias. Our data provide further evidence that serotonergic neurons mediate graft-induced dyskinesias in Parkinson's disease. Achieving a normal striatal serotonin/dopamine transporter ratio following transplantation of fetal tissue or stem cells should be necessary to avoid the development of graft-induced dyskinesias.

MeSH terms

  • Brain Mapping
  • Brain Tissue Transplantation / adverse effects*
  • Corpus Striatum / diagnostic imaging
  • Corpus Striatum / drug effects
  • Corpus Striatum / metabolism*
  • Dihydroxyphenylalanine / analogs & derivatives
  • Dihydroxyphenylalanine / pharmacokinetics
  • Dopamine Plasma Membrane Transport Proteins / metabolism*
  • Dyskinesias / diagnostic imaging
  • Dyskinesias / etiology*
  • Dyskinesias / pathology*
  • Functional Laterality
  • Humans
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Parkinson Disease / pathology
  • Parkinson Disease / surgery
  • Positron-Emission Tomography
  • Serotonin Plasma Membrane Transport Proteins / metabolism*
  • Time Factors
  • Tomography, Emission-Computed, Single-Photon
  • Tropanes / pharmacokinetics

Substances

  • Dopamine Plasma Membrane Transport Proteins
  • Serotonin Plasma Membrane Transport Proteins
  • Tropanes
  • 2-carbomethoxy-8-(3-fluoropropyl)-3-(4-iodophenyl)tropane
  • fluorodopa F 18
  • Dihydroxyphenylalanine