Management of Motor Complications in Parkinson's Disease
Summary
The management of motor complications in Parkinson’s disease centres on balancing sustained dopaminergic stimulation with minimisation of involuntary movements and fluctuations in motor performance. Long-term levodopa therapy remains the cornerstone of symptomatic treatment but is invariably associated with motor fluctuations characterised by alternating periods of optimised mobility (“ON” time) and re-emergent parkinsonian signs (“OFF” time), as well as dyskinesias, which are unintended hyperkinetic movements. Therapeutic strategies include pharmacokinetic optimisation through extended-release formulations of levodopa and adjunctive dopaminergic agents, the introduction of non-dopaminergic modulators targeting glutamatergic signalling and adenosine receptors, and the tailored use of amantadine and its derivatives for antidyskinetic effect. Device-assisted therapies such as continuous infusion of levodopa–carbidopa intestinal gel and subcutaneous apomorphine infusion provide continuous delivery to reduce pulsatile stimulation. Surgical interventions, notably deep brain stimulation of the subthalamic nucleus or globus pallidus interna, are reserved for refractory motor complications. Recent advances focus on individualising regimens, minimising peaks and troughs of drug levels, and exploring novel allosteric modulators and gene therapies to modulate synaptic plasticity within basal ganglia circuits, thereby reducing the burden of motor fluctuations and improving quality of life.
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Management of Motor Complications in Parkinson's Disease publication trend
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Technical terms
Dyskinesia: involuntary, erratic movements often emerging after chronic levodopa therapy.
“On” time: period when Parkinson’s medication provides adequate control of motor symptoms.
“Off” time: interval when the effects of medication wane and parkinsonian signs reappear.
Motor fluctuations: oscillations between “On” and “Off” states reflecting variable drug efficacy.
References
- Effect of the Metabotropic Glutamate Receptor Type 5 Negative Allosteric Modulator Dipraglurant on Motor and Non-Motor Symptoms of Parkinson’s Disease. Cells (2023).
- Amantadine ER (Gocovri®) Significantly Increases ON Time Without Any Dyskinesia: Pooled Analyses From Pivotal Trials in Parkinson's Disease. Frontiers in Neurology (2021).
- Amantadine delayed release/extended release capsules significantly reduce OFF time in Parkinson’s disease. npj Parkinson's Disease (2022).
- A Randomized, Double‐Blind, Controlled Phase II Study of Foliglurax in Parkinson's Disease. Movement Disorders (2022).
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