Levodopa-associated increase of homocysteine levels and sural axonal neurodegeneration

Arch Neurol. 2004 May;61(5):657-60. doi: 10.1001/archneur.61.5.657.


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.

Objectives: To demonstrate associations among daily levodopa/dopa decarboxylase inhibitor intake, total homocysteine plasma (tHcy) levels, and electrophysiologic sural nerve conduction findings.

Design: We performed bilateral assessment of sensory nerve conduction velocity and sensory nerve action potentials and determined tHcy levels.

Patients: 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.

MeSH terms

  • Action Potentials / drug effects
  • Aged
  • Antiparkinson Agents / adverse effects*
  • Axons / drug effects*
  • Axons / pathology
  • Chromatography, High Pressure Liquid
  • Electrophysiology
  • Female
  • Homocysteine / blood*
  • Humans
  • Levodopa / adverse effects*
  • Male
  • Middle Aged
  • Nerve Degeneration / chemically induced*
  • Nerve Degeneration / pathology
  • Neural Conduction / drug effects
  • Parkinson Disease / blood
  • Parkinson Disease / drug therapy
  • Sural Nerve / drug effects*
  • Sural Nerve / pathology


  • Antiparkinson Agents
  • Homocysteine
  • Levodopa