Motor pattern of periodic limb movements in sleep in idiopathic RLS patients G. Plazzi * , R. Vetrugno, S. Meletti, F. Provini Institute of Clinical Neurology, University of Bologna, Via Ugo Foscolo 7, 40123 Bologna, Italy Abstract Objective: Periodic limb movements in sleep (PLMS) are recurrent sleep-related movements that often occur in association with restless legs syndrome (RLS). The purpose of the present study was to examine the pathophysiology of PLMS in patients with idiopathic RLS. Methods: Ten patients with idiopathic RLS who were medication-free or who had withdrawn from medication at least 2 weeks prior to the study underwent an extensive neurophysiological investigation that included nocturnal video-polysomnographic recording (VPSG), EMG recording, and the Multiple Sleep Latency Test (MSLT). Sleep efficiency and PLMS index were calculated during VPSG. Results: All patients had an increased PLMS index, decreased sleep efficiency, and a pathological MSLT score. Leg muscles were the first to be activated, often with alternation of side, and no constant recruitment pattern could be found from one episode of PLMS to another, even in the same patient. No ordinate caudal or rostral spread of the EMG activity was observed. Conclusions: The results suggest that there are different, independent, and unsynchronized generators for PLMS. The direct participation of the cerebral cortex in the origin of PLMS is unlikely, suggesting that abnormal spinal cord hyperexcitability may act as the primary cause of PLMS, triggered by unidentified sleep-related factors. q 2002 Elsevier Science B.V. All rights reserved. Keywords: Restless legs syndrome; Motor pattern 1. Introduction Periodic limb movements in sleep (PLMS) are recurrent sleep-related movements characterized by rapid flexion of the foot at the ankle and partial flexion of the knee, typically associated with a slower extension of the big toe. Similar movements may involve the upper limbs. PLMS often occur associated with the restless legs syndrome (RLS). PLMS last 0.5–5 s [1], appear especially during light sleep (stages 1–2) and relaxed wakefulness, and recur quasi-periodically every 20–40 s [2,3]. Several models have been suggested to explain the patho- physiology underlying PLMS. Though reduced cortical inhibition [4,5] or an impairment of cortical-subcortical motor structures, particularly of motor inhibitory pathways [6], has been reported in RLS, the absence of any cortical potentials preceding the PLMS confirms our own [7] and Trenkwalder et al.’s [8] findings and seems to exclude a direct participation of the cerebral cortex in the origin of the PLMS. Furthermore, PLMS periodic synchronicity with other oscillations that simultaneously involve EEG activity, autonomic functions, and muscle tone suggest a subcortical, probably reticular, site of origin of PLMS [9,10]. Neurophy- siological studies are consistent with a mechanism active at the pontine level or rostral to it [11], and high-resolution functional magnetic resonance imaging in patients with PLMS and RLS confirms a significant activation of the red nucleus and the brainstem [12]. Nevertheless, studies also suggest that PLMS can be directly generated in the spinal cord. In fact, patients undergoing spinal cord anesthe- sia or with progressive paraparesis due to a thoracic spinal cord lesion may present with PLMS, and a propriospinal pattern of PLMS has been suggested recently [13]. Finally, other studies find electrophysiologic and pathologic signs of peripheral axonal neuropathy in RLS patients, suggesting a role of the peripheral nervous system in the pathogenesis of PLMS [7,14–17]. We recently investigated the EMG propagation pattern of PLMS in patients with idiopathic RLS and found that in PLMS, leg muscles were those more frequently involved, often with alternation of side, and that there was no constant recruitment pattern from one PLMS episode to another, even in the same patient. There was no ordinate caudal or rostral spread of the EMG activity, indicating the engage- ment of different, independent and sometimes unsynchro- nized generators for each PLMS. The abnormal spinal cord Sleep Medicine 3 (2002) S31–S34 1389-9457/02/$ - see front matter q 2002 Elsevier Science B.V. All rights reserved. PII: S1389-9457(02)00146-6 www.elsevier.com/locate/sleep * Corresponding author. Tel.: 139-51-585158; fax: 139-51-644-2165. E-mail address: plazzi@neuro.unibo.it (G. Plazzi).