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

Abstract

Background 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. Objective We investigated the effect of continuous dopaminergic stimulation on cortical maladaptive changes related to oral levodopa treatment. Methods 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. Results 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. Conclusions 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

Therapeutic Strategy for Improving Motor Complications of Parkinson’s Disease: Short-Term Levodopa–Carbidopa Intestinal Gel Therapy Using a Nasogastric Tube

“…Our case reinforces the theory that abnormal neuroplasticity of corticostriatal circuits contributes to motor complications and suggests the potential impact of short-term CDS on the aforementioned abnormal cascade changes induced by pulsatile dopaminergic stimulation. Regrettably, our report lacks an assessment of blood/striatal dopamine levels and cortical neuroplasticity, as reported by Kolmančič et al 5 Not all cases with short-term interventions such as DH, rTMS, and LCIG show symptomatic improvement, 2,6 emphasizing the need for research to elucidate factors influencing the duration of short-term intervention effects.…”

“…1,4 It has been reported that LCIG can normalize inappropriate changes in cortical neuroplasticity. 5 Additionally, there are several reports that short-term repetitive transcranial magnetic stimulation (rTMS), directly modulating cortical neuroplasticity, ameliorated motor complications over a certain period. 6 Among these studies, Shirota et al demonstrated the longest-lasting benefits by stimulating the supplementary motor area in 36 PD patients with an average age of 68, a disease duration of 8.5 years, using low-frequency (1Hz) stimulation for 17 minutes, observing motor improvement for 20 weeks.…”