Rate of augmentation and risk factors with long-term follow-up
in Japanese patients with restless legs syndrome
Received: 9 February 2018 /Accepted: 21 May 2018
Springer-Verlag Italia S.r.l., part of Springer Nature 2018
Objectives Preventing augmentation is the critical clinical issue for RLS treatment. As for augmentation in Asian RLS patients,
there have been only four studies and the follow-up durations of these studies were not long. We investigated Japanese RLS
patients with longer duration of treatment in a clinical setting.
Methods This study is a retrospective assessment of 42 RLS patients with follow-up durations of longer than 18 months (78.4 ±
29.2, range 19–139) at two urban sleep centers in Osaka, Japan from May 2004 to April 2014.
Results The mean age of first visit was 63.5 ± 14.1 years old and the estimated age of RLS onset was 47.9 ± 16.5 years old.
Twenty-eight out of 42 patients were female. At initial evaluation, the mean International Restless Legs Scale score (IRLS score)
was 22.0 ± 5.9. Thirty-one of 42 had already visited other clinics before coming to our sleep centers, and the number of clinics
visited was 1.3 ± 0.6. Augmentation developed in two patients (4.8%), and the dosage of dopamine equivalent in patients with
and without augmentation was 12.5 and 18.8 mg vs. 15.8 ± 17.7 mg. In the two RLS patients with augmentation, ferritin was
113.1 and 114.1 ng/mL, respectively, and the number of clinics before coming to our sleep centers was both three.
Conclusions The augmentation rate of Japanese RLS patients from our study is low compared with previous Western and Asian
studies. It might be attributable to racial difference, lower dosage of dopaminergic treatment, and the level of ferritin.
Restless legs syndrome (RLS)
Restless legs syndrome (RLS) is a neurological disease cate-
gorized as a movement disorder with four characteristic symp-
toms: urge to move limbs, worsening at rest or during inactive
conditions, motor relief, and nighttime appearance or worsen-
ing of symptoms. Additionally, RLS is also regarded as a
sleep-related disorder, because it causes severe insomnia and
the symptoms fluctuate according to the circadian rhythm.
Dopaminergic precursors (e.g., levodopa) and agonists
(e.g., pramipexole, ropinirole, rotigotine) have become first-
line treatments for RLS over the past 10–20 years due to their
extraordinary effectiveness in reducing primary symptoms as
well as lowering periodic leg movements during sleep .
However, levodopa was superseded by the longer acting do-
paminergic agonists as the better treatment for RLS because
there were fewer complications than with levodopa. More
recently, new guideline recommended alpha-2-delta ligands
as the first-line treatment of RLS in order to prevent augmen-
The most common serious complication of dopaminergic
treatment of RLS is Baugmentation,^ in which RLS symptoms
appear earlier during the day, or less commonly, extend be-
yond the originally affected limbs . Prevalence of augmen-
tation varied depending on the type and dose of dopaminergic
drugs and the duration and type of study; however, the aug-
mentation rate from studies lasting 2 or 3 years is
* Naoko Tachibana
Center for Sleep-related Disorders, Department of Neurology, Kansai
Electric Power Hospital, 2-1-7, Fukushima,
Osaka, Fukushima 553-0003, Japan
Sleep Medical Center, Osaka Kaisei Hospital, Osaka, Japan
Division of Sleep Medicine, Kansai Electric Power Medical
Research Institute, Osaka, Japan
Division of Neurology, Kansai Electric Power Medical Research
Institute, Osaka, Japan