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

Abstract

With the progression of Parkinson's disease (PD), pulsatile treatment with oral levodopa causes maladaptive changes within basal ganglia-thalamo-cortical circuits, which are clinically expressed as motor fluctuations and dyskinesias. At the level of the motor cortex, these changes may be detected using transcranial magnetic stimulation (TMS), as abnormal corticospinal and intracortical excitability and absent response to plasticity protocols. We investigated the effect of continuous dopaminergic stimulation on cortical maladaptive changes related to oral levodopa treatment. Twenty patients with advanced PD were tested using TMS within 1 week before and again 6 months after the introduction of levodopa-carbidopa intestinal gel. We measured resting and active motor thresholds, input/output curve, short interval intracortical inhibition curve, cortical silent period, and response to intermittent theta burst stimulation. Patients were clinically assessed with Part III and Part IV of the Movement Disorders Society Unified Parkinson's Disease Rating Scale. Six months after the introduction of levodopa-carbidopa intestinal gel, motor fluctuations scores (P = 0.001) and dyskinesias scores (P < 0.001) were reduced. Resting and active motor threshold (P=0.012 and P = 0.015) and x-intercept of input/output curve (P=0.005) were also decreased, while short-interval intracortical inhibition and response to intermittent theta bust stimulation were improved (P=0.026 and P=0.031, respectively). Changes in these parameters correlated with clinical improvement. In patients with advanced PD, switching from intermittent to continuous levodopa delivery increased corticospinal excitability and improved deficient intracortical inhibition and abnormal motor cortex plasticity, along with amelioration of motor fluctuations and dyskinesias. Continuous dopaminergic stimulation ameliorates maladaptive changes inflicted by chronic pulsatile dopaminergic stimulation. © 2022 International Parkinson and Movement Disorder Society.