Ferini_EU Neurology 09/03/2010 11:50 Page 83
Restless Legs Syndrome
Treatment of Restless Legs Syndrome
Luigi Ferini-Strambi and Mauro Manconi
Sleep Disorders Centre, Department of Neuroscience, H San Raffaele Scientific Institute and Vita-Salute San Raffaele University
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 However, some patients fall asleep rapidly but wake up shortly after
condition characterised by uncomfortable and unpleasant sensations with unpleasant leg sensations that force them to get up and walk
in the legs and an urge to move.
1
The symptoms begin or worsen during around in order to alleviate the symptoms.
3
periods of rest or inactivity, and they are relieved by activity.
2
This relief
generally persists for as long as the activity continues. Sleep laboratory investigations have shown that more than 85% of
patients with RLS also experience stereotyped repetitive movements
Another central characteristic of RLS is the worsening of symptoms in once asleep, a condition known as periodic limb movements during
the evening or during the night.
1
Studies that have investigated sleep (PLMS).
3
PLMS are characterised by rhythmical extensions of
circadian patterns in RLS occurrence have shown that the severity of the big toe and dorsiflexions of the ankle with occasional flexions
leg discomfort follows a circadian rhythm, with a maximum occurring of the knee and hip. A PLMS index (number of PLMS per hour of sleep)
after midnight and a minimum occurring at 10:00am.
3
Even if the greater than 15 for the entire night of sleep is considered
underlying neurobiology of RLS is still not fully understood, the most pathological.
1
In addition to PLMS, RLS patients show also PLM during
accredited hypothesis recognises involvement of the diencephalic wakefulness, known as PLMW.
3
A11 dopaminergic neurons.
4
These dopaminergic cells seem to be
able to modulate the nociceptive afferents by means of their RLS can occur in all ethnic backgrounds. Epidemiological studies
projections into the dorsal horns of the spinal cord.
5
Specific lesions have shown that Caucasians are most affected.
7
Most Caucasian
in A11 nuclei of mice induced some features similar to those of surveys show an approximate 10% prevalence, while surveys from
human RLS, with a long latency of sleep, reduced sleep time and south-eastern Europe and Asian populations report much lower
several episodes of standing upright.
5
prevalences. A rate of 3.2% has been reported in Turkey,
8
3.9% in
central Greece
9
and 0.6% in Singapore.
10
In an epidemiological survey
The majority of RLS patients complain of poor sleep.
6
Most patients conducted in the US and five European countries,
11
RLS symptoms of
report difficulty falling asleep since both immobility and circadian any frequency were reported by 7.2% of the general population:
factors facilitate the occurrence of RLS symptoms at bedtime.
3
symptoms occurred at least two times per week and were reported as
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