Continuous Dopaminergic Stimulation Improves Cortical Maladaptive Changes in Advanced Parkinson's Disease

Area of Science:

• Neuroscience
• Neurology
• Biomedical Engineering

Background:

• Parkinson's disease (PD) progression with oral levodopa leads to maladaptive basal ganglia-thalamo-cortical circuit changes.
• These changes manifest as motor fluctuations and dyskinesias, detectable via transcranial magnetic stimulation (TMS) in the motor cortex.

Purpose of the Study:

• To investigate the impact of continuous dopaminergic stimulation on cortical maladaptive changes associated with oral levodopa treatment in Parkinson's disease.
• To assess if continuous levodopa delivery can reverse or mitigate the negative effects of pulsatile dopaminergic stimulation on motor cortex function.

Main Methods:

• Twenty patients with advanced PD underwent TMS assessments before and 6 months after initiating levodopa-carbidopa intestinal gel.
• Evaluated parameters included motor thresholds, input/output curves, short-interval intracortical inhibition, cortical silent period, and response to intermittent theta burst stimulation.
• Clinical assessments used the Movement Disorders Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Parts III and IV.

Main Results:

• Levodopa-carbidopa intestinal gel significantly reduced motor fluctuations (P=0.001) and dyskinesias (P<0.001) after 6 months.
• Cortical excitability markers, including resting motor threshold (P=0.012) and active motor threshold (P=0.015), decreased.
• Intracortical inhibition and motor cortex plasticity, assessed via short-interval intracortical inhibition (P=0.026) and response to intermittent theta burst stimulation (P=0.031), showed significant improvement.

Conclusions:

• Switching to continuous levodopa delivery in advanced PD patients enhances corticospinal excitability and improves deficient intracortical inhibition and motor cortex plasticity.
• Continuous dopaminergic stimulation effectively ameliorates the maladaptive changes induced by chronic pulsatile levodopa treatment.
• These neurophysiological improvements correlate with the observed clinical amelioration of motor fluctuations and dyskinesias.