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Objective: Augmentation of restless legs syndrome (RLS) is a potentially severe side-effect of dopaminergic treatment. Data on objective motor characteristics in augmentation are scarce. The aim of this study was to investigate in detail different variables of leg movements (LM) in untreated, treated, and augmented RLS patients., Methods: Forty-five patients with idiopathic RLS [15 untreated, 15 treated (non-augmented), 15 augmented] underwent RLS severity assessment, one night of video-polysomnography with extended electromyographic montage, and a suggested immobilization test (SIT)., Results: Standard LM parameters as well as periodicity index (PI) and muscle recruitment pattern did not differ between the three groups. The ultradian distribution of periodic leg movements (PLM) in sleep during the night revealed significant differences only during the second hour of sleep (P <0.05). However, augmented patients scored highest on RLS severity scales (P <0.05) and were the only group with a substantial number of PLM during the SIT., Conclusion: This study demonstrates that polysomnography is of limited usefulness for the diagnosis and evaluation of RLS augmentation. In contrast, the SIT showed borderline differences in PLM, and differences on subjective scales were marked. According to these results, augmentation of RLS is a phenomenon that predominantly manifests in wakefulness., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Objective: The objective of this study was to determine the association between the usage of four classes of "at-risk" medications (antidepressants, neuroleptics, antihistamines, and antiemetics with dopamine blockade) and restless legs syndrome (RLS) in dialysis patients within the United States Renal Data System (USRDS)., Methods: This was a case-control design within a national (United States) patient registry of all patients with end-stage renal disease (ESRD) in the USRDS anytime during the period of 1 October 2006 to 31 December 2010, inclusive. A total of 16,165 ESRD patients (3234 cases; 12,931 age-, sex-, and race-matched controls) were studied., Results: All four classes of "at-risk" medications see widespread use among patients in the USRDS. All were associated with increased odds of an RLS diagnosis (range of odds ratios, 1.47-2.28; all p < 0.0001) during the period of observation. Results were unchanged when controlling for time on hemodialysis. Usage of more than one class of medication increased the odds for having RLS., Conclusions: ESRD patients often receive medication intended for relief of conditions associated with their disease, such as depression and psychological issues, pruritus, and gastroparesis; however, such medications may increase the risk of RLS. Given the high prevalence of RLS in ESRD patients, these medications should only be used when their benefits clearly outweigh the risk of development of the troubling and distressing symptoms of RLS., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Background and Purpose: Augmentation is a major problem with dopaminergic therapy for restless legs syndrome (RLS), and predictors of augmentation have not yet been identified. We aimed to analyze the relationship between baseline ferritin level and occurrence of augmentation in a retrospective analysis of a prospective double-blind trial of cabergoline versus levodopa on augmentation in RLS., Patients and Methods: Patients who experienced augmentation were compared to patients who did not experience augmentation., Results: Augmentation symptoms causing premature discontinuation from the study or which were tolerated (n=36, ferritin: 85+59 ng/ml) were associated with lower levels of serum ferritin compared to patients without augmentation (n=302, ferritin: 118+108 ng/ml, p=0.0062)., Conclusions: Ferritin as a marker of iron storage may play an important role in the pathophysiology of RLS and may prove to be a biomarker for the development of augmentation under dopaminergic therapy.

Objectives: Augmentation of symptom severity is the main complication of dopaminergic treatment of restless legs syndrome (RLS). The current article reports on the considerations of augmentation that were made during a European Restless Legs Syndrome Study Group (EURLSSG)-sponsored Consensus Conference in April 2006 at the Max Planck Institute (MPI) in Munich, Germany, the conclusions of which were endorsed by the International RLS Study Group (IRLSSG) and the World Association of Sleep Medicine (WASM). The Consensus Conference sought to develop a better understanding of augmentation and generate a better operational definition for its clinical identification., Design and Methods: Current concepts of the pathophysiology, clinical features, and therapy of RLS augmentation were evaluated by subgroups who presented a summary of their findings for general consideration and discussion. Recent data indicating sensitivity and specificity of augmentation features for identification of augmentation were also evaluated. The diagnostic criteria of augmentation developed at the National Institutes of Health (NIH) conference in 2002 were reviewed in light of current data and theoretical understanding of augmentation. The diagnostic value and criteria for each of the accepted features of augmentation were considered by the group. A consensus was then developed for a revised statement of the diagnostic criteria for augmentation., Results: Five major diagnostic features of augmentation were identified: usual time of RLS symptom onset each day, number of body parts with RLS symptoms, latency to symptoms at rest, severity of the symptoms when they occur, and effects of dopaminergic medication on symptoms. The quantitative data available relating the time of RLS onset and the presence of other features indicated optimal augmentation criteria of either a 4-h advance in usual starting time for RLS symptoms or a combination of the occurrence of other features. A paradoxical response to changes in medication dose also indicates augmentation. Clinical significance of augmentation is defined., Conclusion: The Consensus Conference agreed upon new operational criteria for the clinical diagnosis of RLS augmentation: the MPI diagnostic criteria for augmentation. Areas needing further consideration for validating these criteria and for understanding the underlying biology of RLS augmentation are indicated.

Gamma-hydroxybutyrate (GHB) has re-emerged as a major treatment for narcolepsy. As dopaminergic transmission is clearly involved in the pathophysiology of restless legs syndrome (RLS), and GHB reduces dopamine release, one may hypothesize that RLS may occur in narcolepsy in the presence of GHB. We report a case of narcolepsy with a severe occurrence of typical RLS with GHB, symptoms never previously experienced by the subject and reversible after withdrawal.

Background and Purpose: Restless legs syndrome (RLS) is a movement disorder that frequently results in significant complaints of insomnia. Based on published case reports, it is commonly believed that RLS can be caused or exacerbated by antidepressant agents, thus complicating the treatment of depressed patients who are already prone to sleep disturbances. However, there are no systematic studies demonstrating an association between the clinical diagnosis of RLS and the use of antidepressant medication., Patients and Methods: Retrospective chart review of 200 consecutive patients presenting for evaluation of sleep initiation insomnia at an accredited freestanding sleep disorders center that is part of an integrated health care system., Results: Mean age (+/-SD) of patients was 51.1+/-14.8 years; 60% were women. Fifty-six percent carried a diagnosis of depression, 38% were being treated with antidepressant medication at presentation and 45% met clinical diagnostic criteria for RLS. There were no statistical associations, either by chi(2) analysis or odds ratios, between RLS and antidepressant use or use of any specific class of antidepressant. Positive associations with RLS were found for patients receiving treatment for hypothyroidism and those taking estrogens; a significant negative association was found for patients receiving beta adrenergic antagonists., Conclusions: Although there are anecdotal reports of antidepressant use causing or exacerbating RLS, systematic study of this issue fails to corroborate an association.

Periodic leg movements in sleep (PLMS) unrelated to restless legs syndrome (RLS) are a polysomnographic finding with a controversial clinical value. We describe a patient with isolated periodic leg movements in sleep (without any awake or sleep complaints), who developed severe diurnal RLS symptoms a few months after starting dopaminergic treatment, a phenomenon mimicking augmentation. The diurnal RLS symptoms disappeared after withdrawal of the dopaminergic drugs. Serum ferritin levels were relatively low (31-61 mcg/l; normal: 30-400 mcg/l). Since low levels of ferritin have been implicated in the genesis of RLS, and augmentation is a phenomenon associated with RLS, our findings here suggest that asymptomatic PLMS may have pathogenic mechanisms similar to RLS. Isolated PLMS and RLS could be, at least in some cases, different clinical forms of the same disorder. The conjunction of dopaminergic treatment with low ferritin levels may expose a patient with isolated PLMS to the development of RLS. Discontinuation of dopaminergic drugs in patients with isolated PLMS who develop RLS during the course of the treatment would be a reasonable recommendation.