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Exploring the causes of augmentation in restless legs syndrome

Long-term drug treatment for Restless Legs Syndrome (RLS) patients can frequently result in augmentation, which is the deterioration of symptoms with an increased drug dose. The cause of augmentation, especially derived from dopamine therapy, remains elusive. Here, we review recent research and clin...

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Autores principales: Zeng, Pengyu, Wang, Tiantian, Zhang, Lisan, Guo, Fang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10571710/
https://www.ncbi.nlm.nih.gov/pubmed/37840917
http://dx.doi.org/10.3389/fneur.2023.1160112
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author Zeng, Pengyu
Wang, Tiantian
Zhang, Lisan
Guo, Fang
author_facet Zeng, Pengyu
Wang, Tiantian
Zhang, Lisan
Guo, Fang
author_sort Zeng, Pengyu
collection PubMed
description Long-term drug treatment for Restless Legs Syndrome (RLS) patients can frequently result in augmentation, which is the deterioration of symptoms with an increased drug dose. The cause of augmentation, especially derived from dopamine therapy, remains elusive. Here, we review recent research and clinical progress on the possible mechanism underlying RLS augmentation. Dysfunction of the dopamine system highly possibly plays a role in the development of RLS augmentation, as dopamine agonists improve desensitization of dopamine receptors, disturb receptor interactions within or outside the dopamine receptor family, and interfere with the natural regulation of dopamine synthesis and release in the neural system. Iron deficiency is also indicated to contribute to RLS augmentation, as low iron levels can affect the function of the dopamine system. Furthermore, genetic risk factors, such as variations in the BTBD9 and MEIS1 genes, have been linked to an increased risk of RLS initiation and augmentation. Additionally, circadian rhythm, which controls the sleep–wake cycle, may also contribute to the worsening of RLS symptoms and the development of augmentation. Recently, Vitamin D deficiency has been suggested to be involved in RLS augmentation. Based on these findings, we propose that the progressive reduction of selective receptors, influenced by various pathological factors, reverses the overcompensation of the dopamine intensity promoted by short-term, low-dose dopaminergic therapy in the development of augmentation. More research is needed to uncover a deeper understanding of the mechanisms underlying the RLS symptom and to develop effective RLS augmentation treatments.
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spelling pubmed-105717102023-10-14 Exploring the causes of augmentation in restless legs syndrome Zeng, Pengyu Wang, Tiantian Zhang, Lisan Guo, Fang Front Neurol Neurology Long-term drug treatment for Restless Legs Syndrome (RLS) patients can frequently result in augmentation, which is the deterioration of symptoms with an increased drug dose. The cause of augmentation, especially derived from dopamine therapy, remains elusive. Here, we review recent research and clinical progress on the possible mechanism underlying RLS augmentation. Dysfunction of the dopamine system highly possibly plays a role in the development of RLS augmentation, as dopamine agonists improve desensitization of dopamine receptors, disturb receptor interactions within or outside the dopamine receptor family, and interfere with the natural regulation of dopamine synthesis and release in the neural system. Iron deficiency is also indicated to contribute to RLS augmentation, as low iron levels can affect the function of the dopamine system. Furthermore, genetic risk factors, such as variations in the BTBD9 and MEIS1 genes, have been linked to an increased risk of RLS initiation and augmentation. Additionally, circadian rhythm, which controls the sleep–wake cycle, may also contribute to the worsening of RLS symptoms and the development of augmentation. Recently, Vitamin D deficiency has been suggested to be involved in RLS augmentation. Based on these findings, we propose that the progressive reduction of selective receptors, influenced by various pathological factors, reverses the overcompensation of the dopamine intensity promoted by short-term, low-dose dopaminergic therapy in the development of augmentation. More research is needed to uncover a deeper understanding of the mechanisms underlying the RLS symptom and to develop effective RLS augmentation treatments. Frontiers Media S.A. 2023-09-28 /pmc/articles/PMC10571710/ /pubmed/37840917 http://dx.doi.org/10.3389/fneur.2023.1160112 Text en Copyright © 2023 Zeng, Wang, Zhang and Guo. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Neurology
Zeng, Pengyu
Wang, Tiantian
Zhang, Lisan
Guo, Fang
Exploring the causes of augmentation in restless legs syndrome
title Exploring the causes of augmentation in restless legs syndrome
title_full Exploring the causes of augmentation in restless legs syndrome
title_fullStr Exploring the causes of augmentation in restless legs syndrome
title_full_unstemmed Exploring the causes of augmentation in restless legs syndrome
title_short Exploring the causes of augmentation in restless legs syndrome
title_sort exploring the causes of augmentation in restless legs syndrome
topic Neurology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10571710/
https://www.ncbi.nlm.nih.gov/pubmed/37840917
http://dx.doi.org/10.3389/fneur.2023.1160112
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