Current Knowledge on the Background, Pathophysiology and Treatment of Levodopa-Induced Dyskinesia-Literature Review.

Michał Hutny,Aleksandra Klimkowicz-Mrowiec,Jagoda Hofman,Agnieszka Gorzkowska

doi:10.3390/jcm10194377

Michał Hutny, Aleksandra Klimkowicz-Mrowiec + Show 2 more

Open Access

https://doi.org/10.3390/jcm10194377

Copy DOI

Abstract

Levodopa remains the primary drug for controlling motor symptoms in Parkinson’s disease through the whole course, but over time, complications develop in the form of dyskinesias, which gradually become more frequent and severe. These abnormal, involuntary, hyperkinetic movements are mainly characteristic of the ON phase and are triggered by excess exogenous levodopa. They may also occur during the OFF phase, or in both phases. Over the past 10 years, the issue of levodopa-induced dyskinesia has been the subject of research into both the substrate of this pathology and potential remedial strategies. The purpose of the present study was to review the results of recent research on the background and treatment of dyskinesia. To this end, databases were reviewed using a search strategy that included both relevant keywords related to the topic and appropriate filters to limit results to English language literature published since 2010. Based on the selected papers, the current state of knowledge on the morphological, functional, genetic and clinical features of levodopa-induced dyskinesia, as well as pharmacological, genetic treatment and other therapies such as deep brain stimulation, are described.

Highlights

The criteria were the purpose of the studies—studies describing the involvement of neuroreceptors, genetic and clinical factors in the development of dyskinesias and the corresponding anatomical and functional changes in brain tissue were classified in the background section, while studies focusing on measuring the efficacy and safety of therapeutic strategies in controlling dyskinesias were classified in the treatment section
Dyskinesia in animal models may be very different from dyskinesia in humans, which limits the translation of the results in animal studies to practice in humans
The results of this study showed that preSMA overactivity is one of the factors contributing to the development of dyskinesia, and that Repetitive preSMA transcranial magnetic stimulation (rTMS) exhibits an antidyskinetic effect proportional to the strength of the applied magnetic field [218]

Summary

Introduction

Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. Treatment of Parkinson’s disease (PD) is inseparable from the use of levodopa, l3,4-dihydroxyphenylalanine (L-DOPA). It is a precursor molecule in the synthesis of catecholamines that act as neurotransmitters in nervous system—epinephrine, norepinephrine (NE) and dopamine (DA). Decreased DA levels, associated with a degenerative process in the substantia nigra (SN), are the trigger for the cardinal motor features of PD, such as bradykinesia and rigidity [1]. The first symptoms of PD appear when DA levels in the striatum are reduced by 80%, with a corresponding neuronal DA loss of 60% [2]

Objectives

Methods

Results

Conclusion