Interactions between deep brain stimulation and levodopa in Parkinson's disease

Area of Science:

• Neurology
• Neurosurgery
• Movement Disorders

Background:

• Deep brain stimulation (DBS) is reported to reduce motor fluctuations and dyskinesia in Parkinson's disease (PD) patients.
• Objective quantification of DBS effects on motor fluctuations and levodopa response is lacking.
• The mechanism by which DBS improves motor fluctuations remains unclear.

Purpose of the Study:

• To objectively quantify the impact of globus pallidus interna (GPi) and subthalamic nucleus (STN) DBS on motor fluctuations and dyskinesia in PD.
• To investigate how DBS modifies the therapeutic response to levodopa.

Main Methods:

• Twelve PD subjects (6 GPi DBS, 6 STN DBS) were monitored over two days with DBS on and off, blinded to stimulation status.
• Levodopa pharmacodynamics were assessed via a 2-hour infusion, with DBS on and off under double-blind conditions.
• Motor function was evaluated using tapping speed, walking speed, tremor, and dyskinesia scores.

Main Results:

• DBS improved mean tapping speed and reduced its variability, primarily by increasing trough speed between medication doses.
• Mean walking speed was modestly increased, and tremor scores were reduced.
• DBS enhanced "drug-off" tapping speed but did not alter levodopa's peak response or duration; GPi DBS reduced peak dyskinesia, while STN DBS tended to increase it.

Conclusions:

• Deep brain stimulation objectively reduces motor fluctuations in Parkinson's disease.
• The benefit is achieved by alleviating "drug-off" disability, not by altering levodopa pharmacodynamics.
• Reducing interdose trough disability is a key mechanism for managing motor fluctuations with DBS.