Treatment of Restless Legs Syndrome
Treatment of Restless Legs Syndrome
European Neurological Review, 2009;4(2):83-7
Abstract
Restless legs syndrome (RLS) is one of the most common neurological disorders. It is characterised by an urge to move the legs accompanied by uncomfortable or unpleasant sensations. Symptoms occur predominantly at rest in the evening or at night, and they are alleviated by moving the affected extremity or by walking. Although the aetiopathogenesis of RLS is still unknown, the rapid and dramatic improvement of RLS with dopaminergic compounds suggests a dopaminergic system dysfunction as a basic mechanism. Some studies have shown that rotigotine transdermal patch is efficacious for RLS treatment: using dosages between 1 and 3mg/24 hours, up to >30% of severely affected patients became symptom-free. Similar safety and tolerability to other non-ergot dopamine agonists have been reported, except for skin reactions at the application site. One of the most important problems when treating RLS patients with dopaminergic compounds is augmentation, which is a phenomenon mainly characterised by earlier onset of symptoms. Retrospective evaluation of augmentation with rotigotine showed a value of 1.5% in a six-month placebo-controlled study and of 2.9% in a one-year open trial, which is lower than the percentage observed with the other dopamine agonist compounds with shorter half-lifes.
Keywords
Restless legs syndrome, rotigotine, dopamine agonists
Disclosure: Luigi Ferini-Strambi has received honoraria for serving on scientific advisory boards for Boehringer-Ingelheim, UCB, GlaxoSmithKline, sanofi-aventis and Transcept Pharmaceuticals. Mauro Manconi has no conflicts of interest to declare.
Received: 10 December 2009 Accepted: 17 February 2010
Correspondence: Luigi Ferini-Strambi, Sleep Disorders Centre, Department of Neuroscience, Università Vita-Salute San Raffaele, Via Stamira d’ Ancona 20, 20127 Milan, Italy. E: ferinistrambi.luigi@hsr.it
Support: The publication of this article is funded by UCB Pharma SA. The views and opinions expressed are those of the authors and not necessarily those of UCB Pharma SA.
Restless legs syndrome (RLS) is a common but frequently unrecognised condition characterised by uncomfortable and unpleasant sensations in the legs and an urge to move.1 The symptoms begin or worsen during periods of rest or inactivity, and they are relieved by activity.2 This relief generally persists for as long as the activity continues.
Another central characteristic of RLS is the worsening of symptoms inthe evening or during the night.1 Studies that have investigated circadian patterns in RLS occurrence have shown that the severity of leg discomfort follows a circadian rhythm, with a maximum occurring after midnight and a minimum occurring at 10:00am.3 Even if the underlying neurobiology of RLS is still not fully understood, the most accredited hypothesis recognises involvement of the diencephalic A11 dopaminergic neurons.4 These dopaminergic cells seem to be able to modulate the nociceptive afferents by means of their projections into the dorsal horns of the spinal cord.5 Specific lesions in A11 nuclei of mice induced some features similar to those of human RLS, with a long latency of sleep, reduced sleep time and several episodes of standing upright.5
The majority of RLS patients complain of poor sleep.6 Most patients report difficulty falling asleep since both immobility and circadian factors facilitate the occurrence of RLS symptoms at bedtime.3 However, some patients fall asleep rapidly but wake up shortly after with unpleasant leg sensations that force them to get up and walk around in order to alleviate the symptoms.3
Sleep laboratory investigations have shown that more than 85% of patients with RLS also experience stereotyped repetitive movements once asleep, a condition known as periodic limb movements during sleep (PLMS).3 PLMS are characterised by rhythmical extensions of the big toe and dorsiflexions of the ankle with occasional flexions of the knee and hip. A PLMS index (number of PLMS per hour of sleep) greater than 15 for the entire night of sleep is considered pathological.1 In addition to PLMS, RLS patients show also PLM during wakefulness, known as PLMW.3
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