Periodic limb movements during sleep: a narrative review

Panagis Drakatos; Michelle Olaithe; Dhun Verma; Katarina Ilic; Diana Cash; Yaqoot Fatima; Sean Higgins; Allan H. Young; K. Ray Chaudhuri; Joerg Steier; Timothy Skinner; Romola Bucks; Ivana Rosenzweig

doi:10.21037/jtd-21-1353

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Periodic limb movements during sleep: a narrative review

Journal article

Open access

Peer reviewed

Periodic limb movements during sleep: a narrative review

Panagis Drakatos, Michelle Olaithe, Dhun Verma, Katarina Ilic, Diana Cash, Yaqoot Fatima, Sean Higgins, Allan H. Young, K. Ray Chaudhuri, Joerg Steier, …

Journal of Thoracic Disease, Vol.13(11), pp.6476-6494

2021

DOI: https://doi.org/10.21037/jtd-21-1353

PMID: 34992826

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Abstract

periodic limb movements (PLMs)

sleep

periodic limb movement phenotype (PLM phenotype)

Objective: Using narrative review techniques, this paper evaluates the evidence for separable underlying patho-mechanisms of periodic limb movements (PLMs) to separable PLM motor patterns and phenotypes, in order to elucidate potential new treatment modalities. Background: Periodic limb movement disorder (PLMD) is estimated to occur in 5-8% of the paediatric population and 4-11% of the general adult population. Due to significant sleep fragmentation, PLMD can lead to functional impairment, including hyperactivity and delayed language development in children, and poor concentration and work performance in adults. Longitudinal data demonstrate that those with PLMD are at greater risk of depression and anxiety, and a 4-fold greater risk of developing dementia. PLMD has been extensively studied over the past two decades, and several key insights into the genetic, pathophysiological, and neural correlates have been proposed. Amongst these proposals is the concept of separable PLM phenotypes, proposed on the basis of nocturnal features such as the ratio of limb movements and distribution throughout the night. PLM phenotype and presentation, however, varies significantly depending on the scoring utilized and the nocturnal features examined, across age, and co-morbid clinical conditions. Furthermore, associations between these phenotypes with major neurologic and psychiatric disorders remain controversial. Methods: In order to elucidate potential divergent biological pathways that may help clarify important new treatment modalities, this paper utilizes narrative review and evaluates the evidence linking PLM motor patterns and phenotypes with hypothesised underlying patho-mechanisms. Distinctive, underlying patho-mechanisms include: a pure motor mechanism originating in the spinal cord, iron deficiency, dopamine system dysfunction, thalamic glutamatergic hyperactivity, and a more cortical-subcortical interplay. In support of the latter hypothesis, PLM rhythmicity appears tightly linked to the microarchitecture of sleep, not dissimilarly to the apnoeic/hypopneic events seen in obstructive sleep apnea (OSA). Conclusions: This review closes with a proposal for greater investigation into the identification of potential, divergent biological pathways. To do so would require prospective, multimodal imaging clinical studies which may delineate differential responses to treatment in restless legs syndrome (RLS) without PLMS and PLMS without RLS. This could pave the way toward important new treatment modalities.

Details

Title: Periodic limb movements during sleep: a narrative review
Authors: Panagis Drakatos - King's College London
Michelle Olaithe - The University of Western Australia
Dhun Verma - King's College London
Katarina Ilic - King's College London
Diana Cash - King's College London
Yaqoot Fatima - The University of Queensland
Sean Higgins - St Thomas' Hospital
Allan H. Young - King's College School
K. Ray Chaudhuri - King's College School
Joerg Steier - St Thomas' Hospital
Timothy Skinner - University of Copenhagen
Romola Bucks - The University of Western Australia
Ivana Rosenzweig (Corresponding Author) - King's College London
Publication details: Journal of Thoracic Disease, Vol.13(11), pp.6476-6494
Publisher: AME Publishing Company
Date published: 2021
DOI: 10.21037/jtd-21-1353
ISSN: 2077-6624
PMID: 34992826
Copyright note: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.
Grant note: YF has received funding from the Medical Research Future Fund, National Health and Medical Research Council, Tropical Australian Academic Health Centre, Western Queensland Primary Health Network, Health, and Wellbeing Queensland and Queensland Health.
Organisation Unit: Indigenous and Transcultural Research Centre; Thompson Institute
Language: English
Record Identifier: 991212780102621
Output Type: Journal article

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