title: Levodopa-associated increase of homocysteine levels and sural axonal neurodegeneration.
abstract: BACKGROUND
  Levodopa metabolism via catechol O-methyltransferase increases levels of the neurotoxin homocysteine, which induces an axonal-accentuated degeneration in sensory peripheral nerves in vitro.
  
  
  OBJECTIVE
  To demonstrate associations among daily levodopa/dopa decarboxylase inhibitor intake, total homocysteine plasma (tHcy) levels, and electrophysiologic sural nerve conduction findings.
  
  
  METHODS
  We performed bilateral assessment of sensory nerve conduction velocity and sensory nerve action potentials and determined tHcy levels.
  
  
  METHODS
  Thirty-one levodopa-treated patients with Parkinson disease (PD) and 27 control subjects.
  
  
  RESULTS
  Sensory nerve action potentials significantly (P<.001) differed between PD patients and controls. No differences between sensory nerve conduction velocities of PD patients and controls appeared. We found significant differences in sensory nerve action potentials be-tween PD patients with significantly elevated tHcy levels and controls (P<.001), PD patients with tHcy levels within the reference range and those with elevated levels (P =.001), and PD patients with tHcy levels levels within the reference range and and controls (P =.04). Our sensory nerve conduction velocity results showed no significant differences. There were significant associations between tHcy levels and sensory nerve action potentials (R = -0.52; P =.002) and and sensory nerve conduction velocity (R = -0.47; P =.008). Daily levodopa/dopa decarboxylase inhibitor intake was significantly related to tHcy levels (R = 0.43; P =.02).
  
  
  CONCLUSIONS
  This electrophysiological sign of peripheral neuronal dysfunction may be circumstantial evidence suggesting that, to a certain extent, sensory nerve action potentials are a surrogate marker for the levodopa metabolism-induced elevation of homocysteine levels and the aggravation of the ongoing central neurodegenerative process.
authors.affiliation: Department of Neurology, St Josef Hospital, Ruhr University Bochum, Bochum, Germany. thomas.mueller@ruhr-uni-bochum.de
authors.forename: Thomas
authors.initials: T
authors.lastname: Müller
authors.forename: Kathrin
authors.initials: K
authors.lastname: Renger
authors.forename: Wilfried
authors.initials: W
authors.lastname: Kuhn
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000368:Aged; D000978:Antiparkinson Agents / Q000009:adverse effects*; D001369:Axons / Q000187:drug effects* / Q000473:pathology; D002851:Chromatography, High Pressure Liquid; D004594:Electrophysiology; D005260:Female; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D007980:Levodopa / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D009410:Nerve Degeneration / Q000139:chemically induced* / Q000473:pathology; D009431:Neural Conduction / Q000187:drug effects; D010300:Parkinson Disease / Q000097:blood / Q000188:drug therapy; D013497:Sural Nerve / Q000187:drug effects* / Q000473:pathology
chemical_list: D000978:Antiparkinson Agents; D006710:Homocysteine; D007980:Levodopa