Diagnostic Standards for Dopaminergic Augmentation of Restless Legs Syndrome: Report from a World Association of Sleep Medicine - International Restless Legs Syndrome Study Group Consensus Conference at the Max Planck Institute
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.
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.
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.
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.
"While dopamine agonists have a longer duration of action and an estimated 50% decrease in incidence of augmentation in comparison with dopamine precursors, one third of patients will continue to develop progressive worsening of symptoms on therapy.27,28 With augmentation, symptoms start to occur earlier in the day, become more severe in intensity and may affect other parts of the body, including the arms and trunk.29 The pathophysiology of augmentation remains unclear and treatment is challenging, being largely based on clinical consensus and expert opinion.29 Impulse control disorders, including gambling and compulsive shopping, can also occur in up to 17% of patients, much like in Parkinson’s, which can result in serious social consequences. "
[Show abstract][Hide abstract] ABSTRACT: Gabapentin enacarbil XR is a new extended-release formulation which attempts to overcome the reduced efficacy of shorter-acting gabapentin, with sustained delivery over a 24-hour period. It is a gabapentin prodrug which is efficiently and rapidly converted to gabapentin during active transport throughout the length of the intestine via high-capacity monocarboxylate type 1 nutrient transporters unlike its predecessor, which is absorbed via low-capacity transporters largely confined to the upper intestinal region. Its lack of saturable absorption allows for dose-proportional absorption and hence increased bioavailability. Several clinical trials addressing its efficacy in moderate to severe restless legs syndrome (RLS) demonstrate improvements in the International RLS Rating Scale after a 2-week to 3-month period. Open-label studies of 52 weeks' duration showed maintenance of symptom reduction with once-daily administration of the extended-release formulation. The most commonly reported treatment-emergent adverse effects were somnolence and dizziness. Although the incidence of emergent adverse effects is high, it is comparable with that of gabapentin. No studies thus far have documented augmentation as an issue, unlike that observed with most dopaminergic agents. In addition, both dopamine precursors and agonists have not been shown to increase slow wave sleep or improve overall sleep architecture consistently despite improvement in the periodic leg movement index, in contrast with gabapentin enacarbil. Presently, gabapentin enacarbil has not been approved by the Therapeutic Goods Administration or Medsafe for use in RLS. The cost of this medication may also be a potential barrier for many patients. Future comparative efficacy studies with gabapentin, first-line dopaminergic agents, rotigotine, being the other once daily RLS medication, and pregabalin, the structural analog of gabapentin, will be necessary.
"The dopamine agonist rotigotine, which is administered transdermally, has also shown efficacy for moderate to severe RLS, and may be advantageous in the PD population due to its method of administration and relatively slow release.71,72 While levodopa may also be effective in treatment of RLS, it is associated with increased frequency of side effects, including morning rebound and RLS augmentation.73 Gabapentin may be an effective alternative, especially if pain is a prominent component of the patient’s RLS symptoms.74 "
[Show abstract][Hide abstract] ABSTRACT: Sleep disturbances are among the most common nonmotor complaints of patients with Parkinson's disease (PD), and can have a great impact on quality of life. These disturbances manifest in a variety of ways; for instance, insomnia, sleep fragmentation, and excessive daytime sleepiness. Sleep-related movement disorders such as restless legs syndrome and periodic leg movements may share a common pathophysiology, and occurrence of rapid eye movement behavior disorder may predate the onset of PD or other synucleinopathies by several years. Medications for PD can have a significant impact on sleep, representing a great challenge to the treating physician. Awareness of the complex relationship between PD and sleep disorders, as well as the varied way in which sleep disturbances appear, is imperative for successful long-term management.
Nature and Science of Sleep 12/2011; 3:125-33. DOI:10.2147/NSS.S18897
"Questionnaires for the detection and analysis of sleep problems were all translated into Korean; of these, the Korean Beck's Depression Inventory (K-BDI) had been previously validated. The questionnaires included the Epworth Sleepiness Scale (ESS) for daytime sleepiness (significantly severe daytime sleepiness: ESS total score≥10) ; the K-BDI for mood disorder screening (in men, mild depression: 16-19, moderate depression: 20-23, severe depression≥24; in women, mild depression: 17-20, moderate depression: 21-24, severe depression≥25) ; the Berlin Questionnaire (BQ) for sleep apnea (high risk group score=1, low risk group score=0) ; the Insomnia Severity Index (ISI) for measuring the intensity of insomnia (normal: 0-7 points, subthreshold insomnia: 8-14 points, moderate insomnia: 15-21 points, severe insomnia:>22 points,) ; and the International Restless Legs Syndrome Study Group (IRLSSG) for restless leg syndrome (mild: 1-10 points, moderate: 11-20 points, severe: 21-30 points, very severe: 31-40 points) . "
[Show abstract][Hide abstract] ABSTRACT: This study evaluated the effectiveness and quality of sleep (QoS) in adult patients with nocturnal lower urinary tract symptoms (LUTS) including nocturia and nocturnal polyuria.
A total of 102 patients with nocturia and daytime LUTS were enrolled in this study. All patients completed a questionnaire that included the International Prostate Symptom Score (IPSS), quality of life score (QoL), overactive bladder questionnaire (OABq), and a sleepiness index. The sleepiness index was measured with the Korean Beck Depression Inventory (K-BDI), Insomnia Severity Index (ISI), Epworth Sleepiness Scale (ESS), Berlin Questionnaire (BQ), and the International Restless Legs Syndrome Study Group (IRLSSG). Statistical analyses included the Student's t-test and chi-square test. Differences were considered significant at a p-value of less than 0.05.
Nocturia during sleep was experienced by 68 (66.7%) out of 102 patients. There was no significant association between the nocturia- and the sleep-related scales, but with multiple regression analysis for sex and age, the K-BDI score (p=0.05), IPSS score (p=0.05), and OABq (p=0.02) were significantly higher in patients who woke up to void during sleep. A total of 57 (55.9%) patients diagnosed with overactive bladder with nocturia had severe daytime sleepiness on the ESS questionnaire (p=0.019) and more urgency symptoms on the IPSS questionnaire (p=0.007).
Patients with nocturia had a greater risk of being depressive and felt sleepier during the daytime. LUTS including nocturia and sleep quality closely affected each other. Therefore, clinicians should consider patients' LUTS and sleep problems or QoS as well to provide more satisfying outcomes.
Korean journal of urology 11/2010; 51(11):757-62. DOI:10.4111/kju.2010.51.11.757
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