Targeting the adenosinergic system in restless legs syndrome: A pilot, "proof-of-concept" placebo-controlled TMS-based protocol.

Autor: Lanza G; Oasi Research Institute-IRCCS, Troina, Italy.; Department of Surgery and Medical-Surgical Specialties, University of Catania, Catania, Italy., Salemi M; Oasi Research Institute-IRCCS, Troina, Italy., Mogavero MP; Vita-Salute San Raffaele University, Milan, Italy.; Division of Neuroscience, San Raffaele Scientific Institute, Sleep Disorders Center, Milan, Italy., Catania V; Oasi Research Institute-IRCCS, Troina, Italy., Galeano A; Oasi Research Institute-IRCCS, Troina, Italy., Garifoli A; Oasi Research Institute-IRCCS, Troina, Italy., Lanuzza B; Oasi Research Institute-IRCCS, Troina, Italy., Morreale M; Oasi Research Institute-IRCCS, Troina, Italy., Tripodi M; Oasi Research Institute-IRCCS, Troina, Italy., Cantone M; Neurology Unit, Policlinico University Hospital 'G. Rodolico-San Marco', Catania, Italy., Cappellani F; Ophtalomolgy Unit, Policlinico University Hospital 'G. Rodolico-San Marco', Catania, Italy., Concerto C; Psychiatry Unit, Policlinico University Hospital 'G. Rodolico-San Marco', Catania, Italy., Rodolico A; Psychiatry Unit, Policlinico University Hospital 'G. Rodolico-San Marco', Catania, Italy., Pennisi M; Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, Italy., Bella R; Department of Medical and Surgical Sciences and Advanced Technologies, University of Catania, Catania, Italy., Ferri R; Oasi Research Institute-IRCCS, Troina, Italy.
Jazyk: angličtina
Zdroj: PloS one [PLoS One] 2024 May 10; Vol. 19 (5), pp. e0302829. Date of Electronic Publication: 2024 May 10 (Print Publication: 2024).
DOI: 10.1371/journal.pone.0302829
Abstrakt: 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.
Competing Interests: The authors have declared that no competing interests exist.
(Copyright: © 2024 Lanza et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
Databáze: MEDLINE
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