Original Article Leg movements during wakefulness in restless legs syndrome: Time structure and relationships with periodic leg movements during sleep Raffaele Ferri a,⇑ , Mauro Manconi b , Giuseppe Plazzi c , Oliviero Bruni d , Filomena I.I. Cosentino a , Luigi Ferini-Strambi e , Marco Zucconi e a Sleep Research Centre, Department of Neurology I.C., Oasi Institute for Research on Mental Retardation and Brain Aging (IRCCS), Troina, Italy b Sleep and Epilepsy Centre, Neurocenter of Southern Switzerland, Lugano, Switzerland c Department of Neurological Sciences, University of Bologna, Bologna, Italy d Centre for Pediatric Sleep Disorders, Department of Developmental Neurology and Psychiatry, University of Rome ‘‘La Sapienza’’, Rome, Italy e Sleep Disorders Center, Department of Neurology, Scientific Institute and University Ospedale San Raffaele, Vita-Salute University, Milan, Italy article info Article history: Received 19 July 2011 Received in revised form 25 July 2011 Accepted 31 August 2011 Available online 15 February 2012 Keywords: Periodic leg movements during sleep Periodic leg movements during wakefulness Restless legs syndrome Dopamine agonist Time structure Periodicity Index abstract Background and objective: Approximately one third of patients with restless legs syndrome (RLS) also show periodic leg movements (PLM) during relaxed wake fulness (PLMW). In contrast with the large amount of data published on periodic leg movements during sleep (PLMS), PLMW have received less attention from the scientific community. The objective of this study was to evaluate the correlations/dif- ferences of time–structure and response to a dopamine-agonist between PLMW and PLMS in patients with RLS. Methods: Ninety idiopathic RLS patients and 28 controls were recruited. Subjects underwent clinical and neurophysiological evaluation, hematological screening, and one or two consecutive full-night polysom- nographic studies. A subset of patients received 0.25 mg of pramipexole or placebo before the second recording. Polysomnographic recordings were scored and LM activity was analyzed during sleep and dur- ing the epochs of wakefulness occurring during the first recording hour. Results: RLS patients had higher LM activity during wakefulness than controls, but with a similar period- icity. Even if correlated, the ability of the PLMW index to predict the PLMS index decreased with increas- ing LM activity. Intermovement intervals during wakefulness showed one peak only at approximately 4 s, gradually decreasing with increasing interval in both patients and controls. The effect of pramipexole was very limited and involved the small periodic portion of LM activity during wakefulness. Conclusions: PLMW index and PLMS index were correlated; however, the magnitude of this correlation was not sufficient to suggest that PLMW can be good predictors of PLMS. Short-interval LM activity dur- ing wakefulness and sleep might be linked to the severity of sleep disruption in RLS patients and the dif- ferences between their features obtained during wakefulness or sleep might be relevant for the diagnosis of sleep disturbances in RLS. Ó 2012 Elsevier B.V. All rights reserved. 1. Introduction Formerly reported by Symmonds in 1953 [1], and first clinically described and polysomnographically detailed by Lugaresi et al. in 1965 [2,3], periodic leg movements (PLM) in restless legs syndrome (RLS) now represent one of the most common findings in routine polysomnographic studies. PLM during sleep (PLMS) are repetitive leg jerks characterized by a triple flexion movement at ankle, knee, and hip, which arise from sleep, especially during NREM sleep. According to the standard criteria, leg movements (LM) are scored as PLM when the electromyographic signal derived from the tibialis anterior shows activations longer than 0.5 and shorter than 10 s, sep- arated by an inter-movement interval ranging from 5 to 90 s from each other, and occurring in series of at least four [4,5]. The periodic occurrence represents the most important feature in differentiating PLMS from other physiological LM activity during sleep, while duration and amplitude are not peculiar features. Interesting information has been obtained from the distribution histogram of LM intermovement-intervals in patients with RLS. This distribution has a consistent bimodal profile, showing one first peak at approximately 2–4 s and a second prominent peak cover- ing, especially, the 16–30 s range [6]. PLMS are temporally associ- ated with cortical (electroencephalographic) arousals and autonomic (heart rate variability, arterial blood pressure) activa- tions. However, the pathological role of PLMS in sleep disruption 1389-9457/$ - see front matter Ó 2012 Elsevier B.V. All rights reserved. doi:10.1016/j.sleep.2011.08.007 ⇑ Corresponding author. Address: Sleep Research Centre, Department of Neurol- ogy I.C., Oasi Institute for Research on Mental Retardation and Brain Aging (IRCCS), Via C. Ruggero 73, 94018 Troina, Italy. Tel.: +39 0935 936111; fax: +39 0935 936694. E-mail address: rferri@oasi.en.it (R. Ferri). Sleep Medicine 13 (2012) 529–535 Contents lists available at SciVerse ScienceDirect Sleep Medicine journal homepage: www.elsevier.com/locate/sleep