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PubMed2006

[Restless legs syndrome and psychiatric diseases].

Restless legs syndrome (RLS) is a common sleep disorder characterized by dysesthesias and paresthesias in the legs, occurring at rest, worsening at evening and night and alleviated by movements. Apart from idiopathic cases, RLS and psychiatric diseases share a common association and recent studies have shown a strong association between RLS and antidepressants. The effects of antidepressants such as selective serotonin reuptake inhibitors and venlafaxine on worsening RLS have been widely studied and their use should be avoided. The clinical spectrum of RLS and the physiopathological link with antidepressant will be discussed in this review in order to provide new preventive strategy in clinical practice to improve diagnosis, orientating therapeutic decision and evaluating efficacy of treatment.

Antidepressive Agents↗

PubMed2003

Arm restlessness as the initial symptom in restless legs syndrome.

BACKGROUND: Upper extremity symptoms can develop in restless legs syndrome, but are rarely the initial symptom. OBJECTIVES: To report a case of restless legs syndrome with restless arms as the initial symptom, and to review the literature. DESIGN: Case report and literature review. PATIENT: A 78-year-old man had arm restlessness and sleep disturbance. A polysomnogram demonstrated subclinical periodic leg movements 1 year after the onset of his symptoms. RESULTS: Two years later, he developed lower extremity symptoms that fit the criteria for restless legs syndrome. To our knowledge, this is the first case of restless legs syndrome with arm restlessness as the initial symptom in an otherwise neurologically normal person. CONCLUSION: Restless legs syndrome may initially exhibit upper extremity symptoms.

Aged↗

PubMed2000

Rheumatologic serologies in secondary restless legs syndrome.

Diagnostic criteria for restless legs syndrome (RLS) have been established; however, the pathophysiology of this common condition remains elusive. Several secondary forms of RLS potentially include renal failure, iron deficiency, pregnancy, and neuropathy. RLS has also been reported in approximately 25% of patients diagnosed with rheumatoid arthritis and Sjögren's syndrome. We performed clinical and serologic evaluations on 68 patients diagnosed with RLS to determine how many may have concurrent rheumatologic disease that could be causing their RLS symptoms. We compared these with other postulated secondary causes of RLS. No patient had clinical evidence of rheumatologic disease, and only four had any positive serologic evaluations (two positive SSA/SSB and two mildly elevated RF titers). Three of these had a positive family history for RLS. Patients without a family history of RLS did have lower ferritin levels, more cases of neuropathy, and an older age at symptom onset. We do not think rheumatologic disease represents a significant secondary cause of RLS and do not recommend serologic investigation unless there are overt clinical signs. In contrast, our study suggests that neuropathy and serum iron deficiency do represent secondary forms of RLS.

Adult↗

PubMed2005

Is restless legs syndrome underrecognized? Current management.

Restless legs syndrome (RLS) is a poorly understood sensory-motor neurological disorder whose prevalence in Caucasian populations ranges from 10% to 15%. The patient reports unpleasant sensations in the lower limbs with dysesthesia resulting in an urge to move the legs. The symptoms occur during periods of inactivity, increasing in the evening and at night. Moving the legs provides relief. In 80% of cases, polysomnography shows periodic leg movements during sleep. Patients with idiopathic RLS often report similar symptoms in family members. Secondary RLS may be due to medications, diabetes mellitus, renal failure, iron deficiency, neurological disorders, or rheumatoid arthritis. In secondary RLS, the management rests on treatment of the cause. Symptomatic treatment is warranted in patients with moderate-to-severe symptoms that adversely affect the quality of life. Dopaminergic agents are tried first. When they fail or induce adverse effects, weak opioids, benzodiazepines, anticonvulsants or, if needed, strong opioids, may be used.

Diagnosis, Differential↗

PubMedDate not supplied

The restless legs syndrome: diagnosis and treatment.

Restless leg syndrome (RLS) is a common neurological disorder which can be accompanied with PLMS and can result in sleep disturbance. Greater understanding of pathophysiology of RLS in recent years has led to increased treatment options for this condition. A comprehensive clinical evaluation and appropriate management using combined nonpharmacologic and pharmacologic strategies can result in significant improvement in treatment outcomes in patients with RLS.

Humans↗

PubMed2001

Identification of a major susceptibility locus for restless legs syndrome on chromosome 12q.

Restless legs syndrome (RLS) is a neurological disorder characterized by leg paresthesia associated with an irresistible urge to move that often interferes with nocturnal sleep, leading to chronic sleep deprivation. To map genes that may play a role in the vulnerability to RLS, a genomewide scan was conducted in a large French-Canadian family. Significant linkage was established on chromosome 12q, for a series of adjacent microsatellite markers with a maximum two-point LOD score of 3.42 (recombination fraction.05; P=6x10(-4); autosomal recessive mode of inheritance), whereas multipoint linkage calculations yielded a LOD score of 3.59. Haplotype analysis refined the genetic interval, positioning the RLS-predisposing gene in a 14.71-cM region between D12S1044 and D12S78. These findings represent the first mapping of a locus conferring susceptibility to RLS.

Canada↗

PubMed2004

Restless legs syndrome in 2004.

The restless legs syndrome (RLS) is a sensorimotor disorder characterised by an intense urge to move the legs and sometimes also other parts of the body, and accompanied by a marked sense of discomfort or pain in the affected body parts. This urge has a circadian pattern - it is most pronounced in the evening or during the night. RLS symptoms are relieved by movement. The pathophysiology of RLS is related to dopamine transmission insufficiency, low iron storage in substantia nigra neurons, and spinal cord dysfunction. RLS is idiopathic or secondary (usually associated with iron deficiency, end-stage renal failure, pregnancy and spinal lesions). One half of the patients with idiopathic RLS have positive family history of RLS. RLS is curable, though the choice of therapy and proper dosage titration may take a long time, and though the therapy may sometimes have to be changed owing to augmentation. The most important pharmacologic treatment used in RLS includes L-DOPA, dopamine agonists, opiates, anticonvulsants and benzodiazepines. Therapy improves significantly the condition in long-term at least in 80% of RLS patients.

Humans↗

PubMed1999

Nocturnal eating/drinking syndrome and neuroleptic-induced restless legs syndrome.

Nocturnal eating/drinking syndrome secondary to neuroleptic-induced restless legs syndrome (RLS) occurred under treatment with low-dose haloperidol in a 51-year-old female schizophrenic patient. Polysomnographic investigation showed a low level of sleep efficacy, periodic leg movements, and a strict relationship between nocturnal eating episodes and non-rapid eye movement sleep. Her nocturnal eating and RLS were completely inhibited by clonazepam treatment. To our knowledge, this is the first published case of nocturnal eating/drinking syndrome secondary to neuroleptic-induced RLS.

Antipsychotic Agents↗

PubMed2004

[Restless legs syndrome in childhood].

The diagnostic criteria of restless legs syndrome were defined in 1995 by the International Restless Legs Syndrome Study Group (IRLSSG). In light of the latest scientific evidence and increasing clinical experience, the diagnostic criteria were revised in a consensus workshop. Participants of the workshop considered the development of new diagnostic criteria especially important for the following subgroups: (1) for children and (2) for the cognitively impaired elderly. The common characteristic of both groups lies in their difficulty in expressing subjective symptoms adequately. This considerably impedes the diagnosis of restless legs syndrome. In 2002, a proposal for diagnostic criteria of restless legs syndrome in childhood was formulated by members of the study groups "Movement Disorders and Sleep" and "Paediatrics" of the German Sleep Society. The proposal was partially incorporated into the diagnostic criteria for restless legs syndrome in childhood suggested by the IRLSSG. The current criteria are recommendations to enhance further research and must be validated by clinical studies. The following article gives an overview of published studies on restless legs syndrome in childhood, reviews the proposals for diagnostic criteria, and summarizes the peculiarities to be considered in diagnosing restless legs syndrome in children.

Adolescent↗

PubMed1999

Positron emission tomographic studies in restless legs syndrome.

We studied six restless legs syndrome (RLS) patients with [F18]fluorodeoxyglucose (FDG) positron emission tomography (PET). We also studied four of these same patients with [F18]fluorodopa (FDOPA) PET. The patients' FDG and FDOPA PET scans were compared with those from age-matched healthy control subjects. No significant differences between the two groups were found for any regional blood flow values derived from the FDG scans or for any binding constants derived from the FDOPA scans. These results suggest that any abnormal resting brain metabolic activity or putative presynaptic dopaminergic defect in RLS is likely either to be so subtle that it is below the threshold for ready detection by PET or that it is located in an area of neural tissue inaccessible to the current scanner. No substantial defect is likely to involve the dopaminergic nigrostriatal axis.

Aged↗

PubMed2006

Restless legs syndrome: a clinical update.

Restless legs syndrome (RLS) is a common and often disabling sensorimotor disorder. Epidemiologic studies suggest that RLS is an underrecognized and undertreated disorder affecting both children and adults. The diagnosis is based primarily on the following four essential criteria: (1) an urge to move, usually associated with paresthesias, (2) onset or exacerbation of symptoms at rest, (3) relief of symptoms with movement, and (4) symptoms manifesting in a circadian pattern. Supplemental workup including polysomnography, iron profile, and/or neuropathy screen can provide support for the diagnosis and aid in the treatment strategy. Behavioral techniques, dopaminergic agents, opiates, benzodiazepines, and antiepileptics all have potential value in treating this disorder. Dopaminergic agents continue to be the most effective RLS treatment. However, due to their potential long-term side effects, these agents should not be considered the sole treatment of choice. In the end, the therapeutic plan should be individualized to suit each patient's presentation and needs.

Behavior Therapy↗

PubMed2005

Methadone for refractory restless legs syndrome.

Most cases of restless legs syndrome (RLS) initially respond well to dopaminergic agonists. However, an unknown percentage of patients is intolerant of dopaminergic adverse events, initially or subsequently refractory, or develops limiting augmentation. We administered methadone 5 to 40 mg/day (final dose, 15.6 +/- 7.7) to 29 RLS patients who failed dopaminergics. They were currently taking or had previously tried 5.9 +/- 1.7 (range, 3-9) different medications for RLS and 2.9 +/- 0.8 (range, 2-4) different dopaminergics. Of the 27 patients who met inclusion criteria, 17 have remained on methadone for 23 +/- 12 months (range, 4-44 months) at a dose of 15.5 +/- 7.7 mg/day; 2 dialysis RLS patients died while on methadone, and 8 stopped the treatment (5 for adverse events, 2 for lack of efficacy, and 1 for logistical reasons). All patients who remain on methadone report at least a 75% reduction in symptoms, and none have developed augmentation. Methadone should be considered in RLS patients with an unsatisfactory dopaminergic response.

Adult↗

PubMed2006

Genetics of restless legs syndrome.

Several studies on restless legs syndrome (RLS) have suggested a substantial genetic contribution in the etiology of this sleep disorder. Clinical surveys of idiopathic RLS patients have shown that 40-90% report a positive family history. The clinical features have been compared between familial and sporadic cases and the only difference found was a younger age-at-onset in familial RLS. Despite several reports suggesting a genetic contribution to the etiology of idiopathic RLS, few molecular genetic studies have been carried out attempting to identify genes that can predispose to this disorder. In particular, genes encoding for the GABA A receptor subunits, the gene for the alpha1 subunit of the glycine receptor, and genes involved in dopaminergic transmission and metabolism have been analyzed, however no significant findings have been reported. Genomewide linkage analysis studies using microsatellite markers have identified three loci for RLS: on chromosome 12q, on chromosome 14q and on chromosome 9p. It is important to investigate whether further RLS families show linkage to one of these loci to discuss the contribution of these loci and to provide a prerequisite of a mutational screening and identification of the RLS genes.

Genetic Linkage↗

PubMed1999

Circadian rhythm of periodic limb movements and sensory symptoms of restless legs syndrome.

The symptoms of restless legs syndrome (RLS) worsen while patients are sitting or lying and also worsen at night. The current study was designed to determine if the periodic limb movements (PLMs) and sensory symptoms of RLS are modulated by an independent circadian factor. We recorded sleeping and waking PLMs and waking sensory symptoms in eight volunteers with RLS for 3 successive nights and days, starting with a polysomnographic recording of 2 nights, followed by a third night of sleep deprivation and the day after sleep deprivation. This study showed that both the PLMs and sensory symptoms were worst at night with a maximum for both between midnight and 1:00 AM and a minimum between 9:00 and 11:00 AM. Sleep and drowsiness had a tendency to worsen PLMs and sensory symptoms after the night of sleep deprivation. Circadian temperature curves were normal in all four patients with adequate data collection. The highest PLM counts occurred on the falling phase of the circadian temperature curve whereas the lowest PLM counts occurred on the rising phase of the curve. We conclude that the PLM and sensory symptoms in RLS are influenced by a circadian rhythm, and that the "worsening at night" criterion of the RLS Definition Criteria is, at least in part, distinct from the "worsening while lying or sitting" criterion.

Adult↗

PubMed2006

Circadian changes in CSF dopaminergic measures in restless legs syndrome.

BACKGROUND AND PURPOSE: Restless legs syndrome (RLS) has a circadian component with symptoms being prominent at night. The dopaminergic (DAergic) system, which plays a role in RLS, entails circadian changes that parallel RLS symptom changes. The aim of this study was to look for relative and diurnal differences in DAergic activity. PATIENTS AND METHODS: All RLS subjects were treated prior to their enrollment in the study but were all drug-free for at least 2 weeks prior to evaluation. Cerebrospinal fluid (CSF) collected at 10 p.m. was used to determine DA-related co-factors and metabolites. These were compared to CSF values collected in a previous study at 10 a.m. RESULTS: The only significant finding from the 10 p.m. samples (30 RLS; 22 control) was increased 3-ortho-methyldopa (3OMD) for RLS compared to controls. A comparison of the 10 p.m. to 10 a.m. values (16 RLS; 9 controls) showed small, non-significant diurnal changes for controls but large diurnal changes in tetrahydrobiopterin (BH4), HVA:5HIAA ratio and 3OMD for RLS, with the 10 a.m. sample showing increases in all three CSF factors compared to the 10 p.m. sample. CONCLUSIONS: The greater diurnal changes in RLS suggest greater fluctuations than normal in DAergic circadian dynamics. The increased 3OMD concentration in the absence of concurrent exogenous levodopa (l-dopa) suggests changes in synthesis or metabolism of l-dopa in RLS.

Biopterins↗

PubMed2001

A crossover study of gabapentin in treatment of restless legs syndrome among hemodialysis patients.

Restless legs syndrome (RLS) is a common entity affecting hemodialysis patients. Although the cause of RLS remains unclear, a number of therapies have been used successfully to treat the disorder. Gabapentin is an anticonvulsant shown to alleviate symptoms of RLS in two small studies of nonhemodialysis patients. Because it is excreted renally, gabapentin has a long half-life among hemodialysis patients and may be advantageous if proven effective. We conducted a randomized, double-blind, placebo-crossover study of gabapentin in the treatment of RLS among a population of hemodialysis patients. Sixteen patients identified with RLS were randomized to either gabapentin or placebo. After 6 weeks of treatment with 200 to 300 mg of gabapentin after each hemodialysis session, patients' RLS was reassessed. After a 1-week washout period, patients were switched from gabapentin to placebo or placebo to gabapentin. After another 6 weeks, patients' RLS was assessed again. Patient data were analyzed using both parametric and nonparametric means. Thirteen of the 16 original patients completed the study. Two patients dropped out because of lethargy (believed to be secondary to gabapentin), and 1 patient died secondary to myocardial infarction. Eleven patients responded to gabapentin, but not placebo (P < 0.01). One patient responded to both, and 1 patient responded to placebo, but not gabapentin. Gabapentin is an effective treatment for RLS in hemodialysis patients.

Acetates↗

PubMed2004

Genomewide linkage scan identifies a novel susceptibility locus for restless legs syndrome on chromosome 9p.

Restless legs syndrome (RLS) is a common neurological disorder that affects 5%-12% of all whites. To genetically dissect this complex disease, we characterized 15 large and extended multiplex pedigrees, consisting of 453 subjects (134 affected with RLS). A familial aggregation analysis was performed, and SAGE FCOR was used to quantify the total genetic contribution in these families. A weighted average correlation of 0.17 between first-degree relatives was obtained, and heritability was estimated to be 0.60 for all types of relative pairs, indicating that RLS is a highly heritable trait in this ascertained cohort. A genomewide linkage scan, which involved >400 10-cM-spaced markers and spanned the entire human genome, was then performed for 144 individuals in the cohort. Model-free linkage analysis identified one novel significant RLS-susceptibility locus on chromosome 9p24-22 with a multipoint nonparametric linkage (NPL) score of 3.22. Suggestive evidence of linkage was found on chromosome 3q26.31 (NPL score 2.03), chromosome 4q31.21 (NPL score 2.28), chromosome 5p13.3 (NPL score 2.68), and chromosome 6p22.3 (NPL score 2.06). Model-based linkage analysis, with the assumption of an autosomal-dominant mode of inheritance, validated the 9p24-22 linkage to RLS in two families (two-point LOD score of 3.77; multipoint LOD score of 3.91). Further fine mapping confirmed the linkage result and defined this novel RLS disease locus to a critical interval. This study establishes RLS as a highly heritable trait, identifies a novel genetic locus for RLS, and will facilitate further cloning and identification of the genes for RLS.

Chromosome Mapping↗

PubMed2002

Treating restless legs syndrome: current pathophysiological concepts and clinical trials.

Restless legs syndrome is a distinctive clinical syndrome with a prevalence of about 5% in the general population. One of the outstanding characteristics of restless legs syndrome is its extreme responsiveness to dopaminergic agents. Together with the latest pathophysiological and genetic findings, recent epidemiological and clinical data give a new insight into the classification of restless legs syndrome, thus building the theoretical foundation for the development of new pharmacological methods in its treatment. Current efforts within this area focus on establishing dopaminergic substances for therapy. The hypothesis of a disturbed iron metabolism in restless legs syndrome has been revived by recent theoretical considerations. The present review attempts to explain current strategies of treatment for restless legs syndrome in relation to aetiological, genetic and pathophysiological findings.

Animals↗