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Levodopa-Associated Increase of Homocysteine Levels and Sural Axonal Neurodegeneration
Thomas Müller, MD;
Kathrin Renger, MD;
Wilfried Kuhn, MD
Arch Neurol. 2004;61:657-660.
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.
From the Department of Neurology, St Josef Hospital, Ruhr University Bochum, Bochum, Germany. Dr Kuhn is now with the Department of Neurology, Leopoldina Krankenhaus, Schweinfurt, Germany.
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