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Concept: Restless legs syndrome

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Beyond the cardinal motor symptoms, bradykinesia, rigidity, tremor and postural instability, defining the diagnosis of Parkinson’s disease, there is a big spectrum of non-motor features that patients may suffer from and that may reduce their quality of life. Non-motor symptoms are not only frequent but also often under-reported by patients and caregivers. As they are frequently under-recognized by clinicians, they remain consequently under-treated. This review wants to give a short overview of the importance of non-motor symptoms on patients' quality of life and helpful assessment tools that might facilitate recognition of non-motor features during clinical setting. Given the wide range of non-motor symptoms in Parkinson’s disease, we concentrate on common issues such as depression and sleep disorders like sleep-onset insomnia or sleep maintenance insomnia and restless legs syndrome. Thereby, we present some recent studies that have investigated the efficacy of dopaminergic drugs, especially dopamine agonists, revealing possible treatment strategies and thus improving disease management.

Concepts: Parkinson's disease, Substantia nigra, Dopamine, Haloperidol, Pramipexole, Ropinirole, Restless legs syndrome, Dopamine agonist

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The cutaneous silent period (CSP) is a spinal inhibitory reflex primarily mediated by A-delta fibers. Prolonged CSPs have been reported in patients with restless legs syndrome (RLS) and idiopathic Parkinson’s disease (IPD). Dopaminergic medication normalizes the CSP, concurring with the effect of levodopa on CSPs. To date, CSPs have not been extensively studied in patients with multiple system atrophy (MSA). The purpose of this study was to confirm abnormal CSP findings in a group of MSA patients and to affirm the lack of influence of levodopa on CSPs during long-term treatment.

Concepts: Parkinson's disease, Parkinsonism, Neurotransmitter, Dopamine, Pramipexole, Ropinirole, Restless legs syndrome, Multiple system atrophy

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Persistent insomnia is among the most frequent complaints in general practice. To identify genetic factors for insomnia complaints, we performed a genome-wide association study (GWAS) and a genome-wide gene-based association study (GWGAS) in 113,006 individuals. We identify three loci and seven genes associated with insomnia complaints, with the associations for one locus and five genes supported by joint analysis with an independent sample (n = 7,565). Our top association (MEIS1, P < 5 × 10(-8)) has previously been implicated in restless legs syndrome (RLS). Additional analyses favor the hypothesis that MEIS1 exhibits pleiotropy for insomnia and RLS and show that the observed association with insomnia complaints cannot be explained only by the presence of an RLS subgroup within the cases. Sex-specific analyses suggest that there are different genetic architectures between the sexes in addition to shared genetic factors. We show substantial positive genetic correlation of insomnia complaints with internalizing personality traits and metabolic traits and negative correlation with subjective well-being and educational attainment. These findings provide new insight into the genetic architecture of insomnia.

Concepts: Scientific method, Gene, Genetics, Evolution, Biology, Genome-wide association study, Benzodiazepine withdrawal syndrome, Restless legs syndrome

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Introduction.  Persistent genital arousal disorder (PGAD) is a potentially debilitating disorder of unwanted genital sensation and arousal that is generally spontaneous and unrelenting. Since its first description in 2001, many potential etiologies and management strategies have been suggested. Aim.  To review the literature on PGAD, identify possible causes of the disorder, and provide approaches to the assessment and treatment of the disorder based on the authors' experience and recent literature. Methods.  PubMed searches through July 2012 were conducted to identify articles relevant to persistent sexual arousal syndrome and PGAD. Main Outcome Measures.  Expert opinion was based on review of the medical literature related to this subject matter. Results.  PGAD is characterized by persistent sensations of genital arousal in the absence of sexual stimulation or emotion, which are considered unwanted and cause the patient at least moderate distress. The proposed etiologies of PGAD are plentiful and may involve a range of psychologic, pharmacologic, neurologic, and vascular causes. PGAD has been associated with other conditions including overactive bladder and restless leg syndrome. Assessment should include a through history and physical exam and tailored radiologic studies. Treatment should be aimed at reversible causes, whether physiologic or pharmacologic. All patients should be considered for cognitive therapy including mindfullness meditation and acceptance therapy. Conclusions.  PGAD likely represents a range of conditions manifesting in unwanted genital sensations. Successful treatment requires a multidisciplinary approach and consideration of all reversible causes as well as cognitive therapy. Facelle TM, Sadeghi-Nejad H, and Goldmeier D. Persistent genital arousal disorder: Characterization, etiology, and management. J Sex Med **;**:**-**.

Concepts: Medicine, Sexual intercourse, Causality, The Canon of Medicine, Syndromes, Sexual arousal, Restless legs syndrome, Persistent genital arousal disorder

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Restless legs syndrome is a curious neurological disorder of unknown aetiology. A new study has found that Drosophila mutants in the fly homologue of a human gene, BTBD9, that has been implicated as a risk factor for restless legs display important features of the syndrome.

Concepts: Cell, Chromosome, The Canon of Medicine, Neurology, Epilepsy, Neurological disorder, Restless legs syndrome, BTBD9

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Restless Legs Syndrome (RLS) is estimated to affect 5-15 percent of the U.S. population. There are few studies investigating non-pharmacological treatments for RLS, such as physical therapy and/or peripheral neural mobilization. The traction straight leg raise (tSLR) technique is one such mobilization that may affect central and peripheral neural pathways and reduce RLS symptoms. The purpose of this study is to determine the effects of a tSLR on the symptoms associated with RLS. A cohort of fifteen people was enrolled. Thirteen subjects (11 female) between the ages of 32-64 completed the study. Subjects completed two questionnaires to quantify their severity of RLS before treatment was initiated and at the final session. These measures included: the Restless Legs Syndrome Rating Scale (RLSRS) 0-40, an RLS Ordinal Scale, and a Global Rating of Change (GROC) assessments (-7, 0, +7). Patients were treated with tSLR bilaterally for four total visits on days 1, 3, 8, and 15. Results indicated an RLSRS pre-treatment average of 24.8 (severe) and post-treatment average of 9.2 (mild), representing a 63% improvement from baseline (p < 0.05). Ten of 13 subjects reported a GROC of +4 or higher at the final session, indicating at least a moderate improvement in patient status from baseline. Our results indicate that following a series of tSLR treatments symptoms were reduced in individuals with idiopathic RLS. A prospective, randomized controlled trial is necessary to evaluate the potential for a tSLR to effectively manage idiopathic RLS symptoms.

Concepts: Patient, Randomized controlled trial, Evaluation methods, Syndromes, The Final, Dopamine, Restless legs syndrome, Straight leg raise

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Objective: This post-hoc analysis of a prospective open-label study investigated patients with restless legs syndrome (RLS) taking approved dosages (1, 2 or 3 mg/24 h) of rotigotine transdermal patch for up to 5 years. Research design and methods: Following 6 weeks' double-blind treatment, patients with moderate-to-severe RLS received open-label rotigotine titrated to optimal dosage. Main outcome measures: Safety was assessed by adverse events (AEs) and efficacy was assessed by the International Restless Legs Syndrome Study Group Rating Scale (IRLS). Results: Of 295 patients who entered the open-label study, 198 (67%) began the maintenance period taking rotigotine dosages of 1 - 3 mg/24 h, or increased their dosage from 0.5 mg in the first 3 months of the maintenance period. Of the 198 patients, 45 patients (23%) completed 5 years of follow-up within this dosage range, 79 patients (40%) had their dosage adjusted outside this range during follow-up and 74 patients (37%) withdrew (including 49 [25%] due to AEs and 6 [3%)] for lack of efficacy). Application site reactions were the most common AEs (102 of 198 patients [52%]), with an incidence of 35% (69 of 198) in year 1, 19% (19 of 102) in year 2, and 4 - 6% during each of years 3 - 5. Mean IRLS total score decreased from 27.1 ± 6.0 at double-blind baseline to 6.5 ± 6.5 at the beginning of maintenance, and to 7.4 ± 8.4 after 5 years' treatment on 1 - 3 mg/24 h (n = 45); 21 patients (47%) were classified as symptom-free (IRLS = 0). Conclusions: Consistent with the results for the overall population, rotigotine transdermal patch at approved dosages of 1 - 3 mg/24 h was generally well tolerated after the first year, with sustained efficacy in patients who completed 5 years of treatment at dosages of 1 - 3 mg/24 h.

Concepts: Medical statistics, Syndromes, Harshad number, Pramipexole, Restless legs syndrome, Dopamine agonist, Rotigotine

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Abstract Objective. The aim of this study was to investigate demographic, clinical and psychosocial factors associated with sleep quality in patients on continuous ambulatory peritoneal dialysis (CAPD). Material and methods. Demographic data, clinical and biochemical parameters of 112 CAPD patients (convenience sample of 52 women and 60 men, mean age 51 ± 15 years) were measured. In the same patients, the Pittsburgh Sleep Quality Index (PSQI) was used for assessing sleep quality, the Beck Depression Inventory (BDI) for severity of depressive symptoms, the International Restless Legs Syndrome Study Group criteria for the diagnosis of restless legs syndrome (RLS), and the Short Form-36 (SF-36) of Medical Outcomes Study questionnaire for quality of life (QoL). Results. Patients with PSQI scores of > 5 (“bad sleepers”) had lower serum albumin (p = 0.008), total cholesterol (p = 0.034), normalized protein equivalent of nitrogen appearance (p = 0.046) and residual renal function (p = 0.012), but higher serum ferritin (p = 0.016) and BDI scores (p < 0.001). No significant correlation could be demonstrated between sleep quality and other demographic and clinical parameters. Although the prevalence of RLS was higher in poor sleepers, the difference did not reach statistical significance (p = 0.067). In multivariate analysis, only elevated BDI was an independent predictor of poor sleep quality (p = 0.031). Compared with good sleepers, poor sleepers had significantly lower QoL scores in all subscales of the SF-36. Conclusions.Although poor sleepers had lower nutritional indices, an elevated BDI was the only independent predictor of poor sleep quality. Poor sleep quality was also associated with lower QoL in patients on CAPD.

Concepts: Chronic kidney disease, Nephrology, Dialysis, Peritoneum, Peritoneal dialysis, Restless legs syndrome, Ferritin, Beck Depression Inventory

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Occidental medicine has a given definition for restless legs syndrome (RLS) and knowledge of RLS pathophysiology has led to the development of its therapeutic management. RLS has no cure. Many methods have been used for its treatment, among which traditional Chinese medicine (TCM) has been considered as a new approach. However, description and management of the disease symptoms can be found in Chinese ancient medical systems. The first mention of RLS may have been as early as the third century BC described as “leg uncomfortable”. Nonetheless, the lack of a complete description encompassing all four modern cardinal features of RLS makes this uncertain. On the other hand, the first description of RLS encompassing three of the four major modern criteria occurs in the ancient book of Neike Zhaiyao (Internal summary), 1529 AD just about a century and a half prior to the description of RLS by Sir Thomas Willis in England. Here, we introduce the philosophical concepts of traditional Chinese medicine and the description, classification and understanding of RLS symptoms in traditional Chinese medicine. We have conducted an in-depth review of the literature reporting one part of TCM, Chinese herbal treatment efficacy for RLS, through both English and Chinese search engines. Eighty-five studies were included in the review and more than 40 formulas (including 176 different ingredients) were found in the literature. According to the literature, Chinese herbs have been demonstrated to be safe and hold great potential to be an effective treatment modality for RLS, but the evidence is limited by the quality of these studies. Of the eighty-five studies, only nine were clinical trials with a control group and only three of them were randomized. In cases where herbal preparations were compared to Western medications for RLS, the herbal preparations appear to be superior. However, uncertainty as to whether the diagnosis of RLS was made in accord with Western norms and the use of homemade non-validated rating scales create uncertainty as to the meaning of these results. High-quality randomized and double blinded clinical trials of Chinese herbs in treating RLS will be required in the future. This review highlights aspects of Chinese herbal treatment important to guide future research and clinical practice. To our knowledge, this is the first systematic English review of the role of Chinese herbs in the treatment of RLS.

Concepts: Clinical trial, Alternative medicine, Herbalism, Traditional Chinese medicine, Restless legs syndrome, Chinese herbology, Chinese classic herbal formula, Li Shizhen

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OBJECTIVES: Sleep disorders, especially restless legs syndrome (RLS) and rapid eye movement sleep behavior disorder (RBD), are common in spinocerebellar ataxia type 3 or Machado-Joseph disease (MJD), and a possible underlying dopaminergic dysfunction is implicated. This study assessed the relationship between sleep disorders in MJD and dopamine transporter (DAT) densities. PATIENTS AND METHODS: Twenty-two patients with MJD and twenty healthy subjects were enrolled in this study. MJD patients underwent clinical sleep evaluation and polysomnography. SPECT with [(99m)Tc]-TRODAT-1, was performed in all subjects. RESULTS: DAT densities were significantly reduced in MJD group when compared to controls. No significant correlation was found between DAT densities and RLS or RBD in MJD. CONCLUSION: Our study failed to demonstrate a clear correlation between sleep disorders and DAT densities in MJD patients, hence suggesting that extrastriatal and non-presynaptic dopamine pathways could be implicated in MJD-related sleep disorders.

Concepts: Sleep, Dopamine, Rapid eye movement sleep, Spinocerebellar ataxia, Pramipexole, Restless legs syndrome, Machado-Joseph disease, Periodic limb movement disorder