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© 2024 Lanza et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.

Abstract

Restless Legs Syndrome (RLS) is a common sleep disorder characterized by an urge to move the legs that is responsive to movement (particularly during rest), periodic leg movements during sleep, and hyperarousal. Recent evidence suggests that the involvement of the adenosine system may establish a connection between dopamine and glutamate dysfunction in RLS. Transcranial magnetic stimulation (TMS) is a non-invasive electrophysiological technique widely applied to explore brain electrophysiology and neurochemistry under different experimental conditions. In this pilot study protocol, we aim to investigate the effects of dipyridamole (a well-known enhancer of adenosinergic transmission) and caffeine (an adenosine receptor antagonist) on measures of cortical excitation and inhibition in response to TMS in patients with primary RLS. Initially, we will assess cortical excitability using both single- and paired-pulse TMS in patients with RLS. Then, based on the measures obtained, we will explore the effects of dipyridamole and caffeine, in comparison to placebo, on various TMS parameters related to cortical excitation and inhibition. Finally, we will evaluate the psycho-cognitive performance of RLS patients to screen them for cognitive impairment and/or mood-behavioral dysfunction, thus aiming to correlate psycho-cognitive findings with TMS data. Overall, this study protocol will be the first to shed lights on the neurophysiological mechanisms of RLS involving the modulation of the adenosine system, thus potentially providing a foundation for innovative “pharmaco-TMS”-based treatments. The distinctive TMS profile observed in RLS holds indeed the potential utility for both diagnosis and treatment, as well as for patient monitoring. As such, it can be considered a target for both novel pharmacological (i.e., drug) and non-pharmacological (e.g., neuromodulatory), “TMS-guided”, interventions.

Details

Title
Targeting the adenosinergic system in restless legs syndrome: A pilot, “proof-of-concept” placebo-controlled TMS-based protocol
Author
Lanza, Giuseppe  VIAFID ORCID Logo  ; Salemi, Michele  VIAFID ORCID Logo  ; Mogavero, Maria P  VIAFID ORCID Logo  ; Catania, Valentina; Galeano, Annalisa; Garifoli, Angelo; Bartolo Lanuzza; Morreale, Manuela; Tripodi, Mariangela; Cantone, Mariagiovanna  VIAFID ORCID Logo  ; Cappellani, Francesco; Concerto, Carmen; Rodolico, Alessandro  VIAFID ORCID Logo  ; Pennisi, Manuela; Bella, Rita; Ferri, Raffaele  VIAFID ORCID Logo 
First page
e0302829
Section
Study Protocol
Publication year
2024
Publication date
May 2024
Publisher
Public Library of Science
e-ISSN
19326203
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
3069286082
Copyright
© 2024 Lanza et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.