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Prevalence, severity and risk factors of restless legs syndrome in the general adult population in two Scandinavian countries.

BACKGROUND AND PURPOSE: To estimate prevalence and severity (using the International Restless Legs Syndrome Study Group Rating Scale (IRLS)) and to identify risk factors of restless legs syndrome (RLS). PATIENTS AND METHODS: Population-based cross-sectional study; 2005 randomly selected adults 18 years and above participated in a telephone interview in Norway and Denmark, employing the next-birthday technique. RESULTS: Of the cross-section, 11.5% fulfilled the diagnostic criteria for RLS. Half of these reported the symptoms as moderate to very severe. Mean duration of the complaint was 10 years. Prevalence was higher in females than in males (13.4 vs 9.4%) and lowest in the youngest age group (18-29 years, 6.3%). From 30 years and above, no clear age-related difference was seen. Main predictors of RLS were insomnia (odds ratios: 1.71-3.16) and symptoms of periodic limb movements in sleep (3.20-7.85). The response rate was 47%, making the results less reliable. CONCLUSIONS: This study indicates that there is a high occurrence of RLS among adults. Main predictors are insomnia and periodic limb movements in sleep.

Adult↗

Simultaneous assessment of posture and limb movements (e.g., periodic leg movements) with calibrated multiple accelerometry.

This study describes new applications for the method of calibrated multiple accelerometry, which detects posture and distinct motion patterns, and limb movements continuously. The aim of our study was to evaluate this assessment technique in terms of its suitability for exploring the relationships between pathological limb movement activity (e.g., periodic leg movements) and posture. The new method proved to be appropriate for the simultaneous assessment of pathological leg jerks and posture and provided a means to revealing possible relations. Generally, our study demonstrates the application of this (ambulatory) assessment technique in the field of sleep and neurological disorders.

Adult↗

Restless legs syndrome and periodic limb movement disorder in the elderly.

Restless legs syndrome (RLS) is a sensorimotor neurological disorder characterized by an urge to move the extremities, mostly the legs, caused or accompanied by unpleasant sensations in the affected limbs. Symptoms appear or increase in the evening or during the night and at rest. Sleep disturbances are the most frequent reason why patients seek medical aid. The diagnosis of periodic limb movement disorder (PLMD) requires polysomnographic confirmation and relies on the exclusion of other causes of sleep disturbances. The diagnosis of RLS is a clinical one and usually based on the patient's history. Diagnosis criteria should be applied in a modified form in the cognitively impaired elderly. The newly revised criteria emphasize behavioral indicators and supportive features in diagnosing RLS in this special population. Prevalence of both disorders increases strongly with age. Epidemiological studies revealed a 9% to 20% prevalence of RLS and an estimated 4% to 11% prevalence of PLMD in the elderly. Recent studies indicate RLS occurring approximately twice as often in older women than in older men. Treatment with dopaminergic drugs, opioids, anticonvulsants or hypnotics are usually well tolerated in the elderly. However, interaction with other medications and the possibility of severe sedation due to slower metabolism in the elderly should be considered.

Aged↗

Can periodic limb movement disorder be diagnosed without polysomnography? A case-control study.

OBJECTIVES: (1) To determine whether clinical information can predict the presence of periodic limb movement disorder (PLMD). (2) To examine whether clinical data correlate with PLMD severity. METHODS: Sixty-one adult patients (48 males and 13 females, aged 55.1+/-14.1 years) with PLMD (without a clinical diagnosis of restless legs syndrome) were compared with 61 control patients without PLMD (43 males and 18 females, aged 49.6+/-16.1 years) in this case-control study. All patients completed a detailed questionnaire which included (1) demographics, (2) sleep complaints, (3) medical disorders, (4) use of medication, nicotine, and caffeine, and (5) history of nocturnal motor/sensory leg symptoms. All patients underwent standard polysomnography. RESULTS: The PLMD and control groups were similar in the prevalence of insomnia, hypersomnia, diabetes, peripheral neurologic disorders, anemia, spinal disease, antidepressant medication use, smoking, caffeine intake, and leg pain. Compared with the control group, the PLMD group reported more leg kicks (28% vs. 5%, P<0.001) and more crawling or aching sensations in legs (28% vs. 11%, P=0.023). The logistic regression analysis showed that only age (P=0.044), leg kicks (odds ratio (OR) 12.70, 95% confidence interval (CI) 2.80-57.63, P=0.001), and crawling or aching in legs (OR 5.23, 95% CI 1.16-23.44, P=0.029) were significantly related to the presence of PLMD. The positive predictive value of leg kicks in the diagnosis of PLMD was 85% and the negative predictive value was 57%. Within the PLMD group, only age correlated positively with the PLM-index (r=0.47, P<0.001). Both the PLM-index and the PLM arousal-index were negatively correlated with sleep efficiency on polysomnography (P=0.005 and P=0.006, respectively). CONCLUSIONS: Clinical data are not sufficiently predictive of the presence of PLMD to rule in or rule out the diagnosis. Polysomnography is required for establishing the diagnosis of PLMD in patients with insomnia or hypersomnia.

Case-Control Studies↗

Inhibition of platelet MAO-B by kava pyrone-enriched extract from Piper methysticum Forster (kava-kava).

Kava-kava, a psychoactive beverage, induces relaxation, improves social interaction, promotes sleep and plays an important role in the sociocultural life in the islands of the South Pacific. On the other hand, standardized extracts of kava-kava roots are used for the therapy of anxiety, tension and restlessness. Kava pyrones, the major constituents of kava kava, are generally considered to be responsible for the pharmacological activity in humans and animals. To obtain more information on the mechanisms by which kava-kava exerts psychotropic properties we investigated the in vitro effects of kava-kava extract and pure synthetic kava pyrones on human platelet MAO-B, in comparison to amitriptyline, imipramine and brofaromine. Kava-kava extract was found to be a reversible inhibitor of MAO-B in intact platelets (IC50 24 microM) and disrupted platelet homogenates (IC50 1.2 microM). Structural differences of kava pyrones resulted in a different potency of MAO-B inhibition. The order of potency was desmethoxyyangonin > (+/-)-methysticin > yangonin > (+/-)-dihydromethysticin > (+/-)- dihydrokavain > (+/-)-kavain. The two most potent kava pyrones, desmethoxyyangonin and (+/-)-methysticin displayed a competetive inhibition pattern with mean Ki 0.28 microM and 1.14 microM respectively. The inhibition of MAO-B by kava pyrone-enriched extracts might be an important mechanism for their psychotropic activity.

Amitriptyline↗

Restless legs syndrome: an historical note.

The article briefly summarizes the milestones leading to current knowledge and the possibility of treating one of the most widespread and perhaps least known diseases, restless legs syndrome (RLS). Until the mid-twentieth century, the syndrome first described by Willis (1685), was sporadically reported in medical literature and in most cases deemed a bizzare condition. It was only with Ekbom's detailed clinical description of the syndrome (1944) and the polygraphic recordings of Coccagna et al. (1962) that RLS became well-recognised clinical entity. Since then, almost all sleep laboratories have devoted much of their research to discovering the pathogenetic mechanisms underlying the disease and devise increasingly specific treatment. Major advances have been made in recent years, but a full understanding of RLS is still a long way off.

History, 17th Century↗

Transient restless legs-like syndrome as a complication of opiate withrawal.

In most cases, restless legs syndrome (RLS) is an idiopathic disorder affecting patients of middle and older age. Usually, the intensity of symptoms is constant or progressive. Here, we describe two opiate addicts developing RLS during opiate withdrawal. Their RLS disappeared along with the remission of withdrawal symptoms. Both cases responded well to a treatment with Madopar (L-dopa plus benserazid). This observation encouraged us to perform a retrospective analysis of all cases of opiate addicts detoxified in our unit during a 5-month period. This analysis revealed 15 out of 120 patients who had described the symptoms of transient RLS emerging during opiate detoxification treatment. Transient RLS during opiate detoxification merits further interst in order to improve the treatment of sleep disturbances during detoxification and as a model of interaction of the dopaminergic and endorphine system in motor activity.

Adult↗

Restless legs syndrome.

PURPOSE: The signs and symptoms, epidemiology, etiology, pathophysiology, diagnosis, pharmacologic and nonpharmacologic treatments, and options and guidelines for the treatment of restless legs syndrome (RLS) are reviewed. SUMMARY: RLS was first described in the 17th century and further characterized in 1945. RLS is a common disorder, occurring in about 10% of the population. Patients with RLS often describe the urge to move, uncomfortable sensations, and pain, which begin or worsen during rest or inactivity such as lying or sitting. Symptoms of RLS make sleeping difficult for many patients, and significant daytime difficulties result from the condition. RLS can either be primary or arise from secondary causes that lead to iron deficiency. There is a familial component in primary RLS, but its underlying mechanisms remain unknown. Of individuals with conditions associated with iron-deficiency states, including pregnancy, renal failure, and anemia, 25-30% may develop RLS. The goals of RLS treatment include improving its symptoms and the patient's quality of life. There are limited data on the treatment of RLS. Pharmacologic therapies include iron replacement, dopaminergic agents (e.g., levodopa), dopamine agonists, anticonvulsants, opioids, and benzodiazepines. There have been no systematic trials of nonpharmacologic therapies for RLS, but good sleep hygiene and avoidance of alcohol, caffeine, and nicotine may improve symptoms. CONCLUSION: RLS is a common disorder thought to involve abnormal iron metabolism and dopaminergic systems. Nonpharmacologic therapy should be suggested for all patients with RLS, but pharmacologic therapy may be required, and evidence is strongest for levodopa and dopamine agonists.

Analgesics, Opioid↗

[The restless legs syndrome can be treated with dopamine agonists].

In three patients, a man aged 46 years and two women aged 74 and 38 years, respectively, restless legs syndrome (RLS) was diagnosed. The second patient had a low serum ferritin concentration. The patients were successfully treated with ropirinol, iron suppletion and gabapentine, and pramipexol, respectively. With a prevalence of 7% in the general population, RLS is a frequent disease. Patients complain about unpleasant feelings in the legs and have an urge to move the legs, causing discomfort during rest. Sleep is disturbed significantly, which interferes with normal functioning of the patients during the day. RLS may be caused by anaemia, uraemia or as a side effect of drugs such as selective serotonin uptake inhibitors (SSRIs), lithium and tricyclic antidepressants. RLS can be treated successfully by dopaminergic agents, especially dopamine agonists.

Adult↗

Periodic limb movement disorder in neuroleptic-induced akathisia.

We recorded all-night polysomnograms of four schizophrenic patients with neuroleptic-induced akathisia (NIA) before and during treatment with clonazepam. Also, four non-akathitic schizophrenic patients were recorded all-night polysomnograms as control subjects. Daily treatment with 1.5 to 3 mg clonazepam improved subjective complaints of all the 4 patients with NIA. Three of 4 patients with NIA exhibited periodic limb movements (PLM) on bilateral legs, but none of 4 control subjects showed PLM. Total number of PLM and PLM per hour decreased during clonazepam treatment. Moreover, mean inter-movement intervals of PLM of 3 patients were prolonged on bilateral legs. NIA might change its feature as PLM during night sleep.

Adult↗

Pramipexole for the treatment of restless legs syndrome.

Restless legs syndrome (RLS) is a common disorder that is estimated to affect 10% of Americans. However, it remains largely undiagnosed and untreated by clinicians. The primary symptoms of this condition are leg discomfort or an urge to move that is temporarily relieved by movement and is worse at rest and at bedtime. RLS impacts the quality of life of the sufferer by disrupting sleep and disturbing or curtailing work and social activities. Approximately 80% of RLS sufferers also have periodic limb movements during sleep, in which repetitive leg movements fragment sleep and may result in daytime drowsiness. RLS may be treated by dopaminergic agents, benzodiazepines, anticonvulsants and opiates; dopamine agonists are currently considered first-line therapy for this condition. Pramipexole has been studied in the treatment of RLS since 1998. This article reviews the role of this medication in the management of this serious neurological disorder.

Adult↗

Snoring and excessive daytime sleepiness in Parkinson's disease.

Recent recognition of daytime sleepiness in Parkinson's disease (PD) has prompted a search for its causes. Sleepy patients may be more susceptible to sleep attacks after the use of dopamine agonists and the recognition of sleep disturbances in PD may influence important therapeutic decisions. To identify clinical factors influencing excessive daytime sleepiness (EDS) and sleep complaints in PD, we studied 86 consecutive patients with clinical diagnosis of PD using a sleep questionnaire, the Epworth Sleepiness Scale, the Unified Parkinson's Disease Rating Scale and the Montgomery and Asberg Depression Rating Scale. Patients with cognitive dysfunction were not included in the study. We found that 49 patients (53.3%) had insomnia, 45 (49.9%) restless legs syndrome (RLS), 51 (55.4%) vivid dreams, 61 (71.8%) snoring and 29 (31.5%) had EDS. RLS was more frequent in patients with longer duration of illness. Snoring was the most important risk factor associated with EDS (OR=3.64, 95% CI=1.11-11.9, P=0.03) and a marginal association between motor dysfunction and EDS was observed (OR=1.06, 95% CI=1.00-1.12, P=0.05).

Adult↗

Moderate to severe periodic limb movement disorder in childhood and adolescence.

The purpose of this study is to review clinical features of children with moderate to severe Periodic Limb Movement Disorder (PLMD). Because of our interest in both Restless Legs Syndrome (RLS) and Attention-Deficit Hyperactivity Disorder (ADHD), many of our patients had one or both of these conditions. We did a retrospective review of 129 children and adolescents who were found to have Periodic Limb Movements in Sleep (PLMS) > 5/hour of sleep. Sixty five had PLMS of 5-10/hour of sleep, 48 had PLMS of 10-25/hour of sleep and 16 had PLMS > 25/hour of sleep. One hundred and seventeen of the original 129 had ADHD. Stimulant medication did not seem to play a role in the production of PLMS. In only 25 of the 129 cases did parents note the presence of PLMS before being specifically asked to look, and even after specific instructions to look, PLMS were not noted by the parents in 39 patients. The sub-group of 16 children and adolescents--6 female, 10 male (average age 11.1 years--range 6-17 years) with moderate to severe PLMS > 25/hour of sleep are described in more detail. Fifteen of the 16 patients had ADHD. Four of the 16 had RLS and 10 of 13 patients for whom a family history was available had a parent with RLS. Two of the 16 patients had their PLMS initially misdiagnosed as seizures. Sleep disturbance was present in all 16 patients and 7 of the 16 had daytime somnolence which resolved with dopaminergic medications. To our knowledge this is the first clinical series of moderate to severe PLMS in children and adolescents to be fully described in the literature.

Adolescent↗

[Continuous sedation for regional anesthesia with propofol (Disoprivan) and midazolam (Dormicum). A comparative study].

UNLABELLED: Propofol was compared to midazolam with regard to its quality as a sedative in regional anesthesia. 81 patients undergoing varicose-vein stripping under epidural anesthesia were divided into two groups: 39 were given propofol and 42 were given midazolam. Both groups were then subdivided into 3 subgroups. 30 min after epidural block, a bolus of propofol 1 mg/kg or midazolam 0.03 mg/kg was given followed by infusion of equipotent solutions: propofol 1.0, 1.5, or 2.0 mg/kg/h or midazolam 0.03, 0.045, 0.06 mg/kg/h. Continuous registration of blood pressure, respiratory rate, and end-expiratory pCO2 was carried out and blood gas analysis was performed every 30 min. RESULTS: Clinically unimportant changes of circulatory and respiratory parameters were seen. Blood gas analyses showed hypercapnia greater than 50 mmHg in some patients. Brief apnea occurred after bolus propofol in 7.7% of cases and pain during injection in 66.6%. Restlessness: propofol 28.2%, midazolam 9.5%. Upper airway obstruction: propofol 30.8%, midazolam 57.1%. Recovery time after infusion ranged from 130 s with propofol to 26 min with midazolam. Postoperative evaluation included the following questions and responses: Sedation pleasant? propofol 97.5%, midazolam 100%. Sleep during surgery? propofol 94.8%, midazolam 83.5%. Prolonged tiredness? propofol 25.6%, midazolam 69%. Postoperative nausea? propofol 38.5%, midazolam 14.2%. Vomiting? propofol 17.9%, midazolam 11.9%. Our study showed that propofol is highly suitable as a sedative for regional anesthesia in spite of injection pain and frequent postoperative nausea. It is superior to midazolam because of the significantly shorter recovery time, providing improved control-lability and reduced posthypnotic sleep.

Anesthesia, Conduction↗

The treatment of restless legs syndrome with intravenous iron dextran.

BACKGROUND AND PURPOSE: To evaluate the safety and efficacy of a single 1000 mg iron infusion in treating Restless Legs Syndrome (RLS). PATIENTS AND METHODS: A single 1000 mg intravenous (IV) [Am J Med Sci 31 (1999) 213] infusion of iron dextran was evaluated in an open-label study. Primary outcomes of efficacy were symptom severity assessed by global rating scale and periodic leg movements in sleep (PLMS) at 2 weeks post-infusion. Secondary outcomes included total sleep time (TST), hours/day of RLS symptoms, and changes in magnetic resonance imaging (MRI)-determined iron concentrations in the substantia nigra. Primary safety measures were reported adverse events and monthly serum ferritin levels. RESULTS: IV iron therapy significantly improved the mean global RLS symptom severity, TST, hours with RLS symptoms and PLMS, but on an individual basis failed to produce any response in 3 of the 10 subjects who were fully treated. Brian iron concentrations at 2 weeks post-infusion as determined by MRI were increased in the substantia nigra and prefrontal cortex. Serum ferritin levels showed a greater than predicted rapid linear decrease. Side effects were mild, except in one subject who developed an acute allergic reaction. CONCLUSIONS: The results in this study provide valuable information for future studies, but the efficacy and safety of IV iron treatment for RLS remain to be established in double-blind studies. The serum ferritin results suggest that greater than expected iron loss occurs after IV iron loading.

Aged↗

A review of pramipexole and its clinical utility in Parkinson's disease.

Parkinson's disease (PD) is a common neurodegenerative disorder characterised by selective loss of dopaminergic neurones in the substantia nigra and resulting in progressive disability. Therapy has focused on replacing depleted dopamine (DA) via supplementation with levodopa or DA agonists. Pramipexole (Mirapex), Pharmacia Corp.) has recently been approved for the treatment of PD. Evidence from preclinical studies and clinical trials have proven the effectiveness of this agent in ameliorating the symptoms of PD. There is also non-human evidence that pramipexole may be neuroprotective and could therefore possibly slow disease progression; however, this has yet to be proven in humans. The use of pramipexole may be limited by its side effect profile compared to standard therapies and its relatively higher cost compared to levodopa. Despite these concerns, pramipexole does have a role in the treatment of PD in all stages of the illness and may arguably be the treatment of choice in early disease. In addition to its use in PD, pramipexole has shown some utility in the treatment of restless legs syndrome (RLS), depression and schizophrenia.

Animals↗