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Restless legs syndrome: keys to recognition and treatment.

Restless legs syndrome (RLS) is a common and clinically significant motor disorder increasingly recognized by physicians and the general public, yet still underdiagnosed, underreported, and undertreated. Effective therapies are available, but a high index of suspicion is required to make the diagnosis and start treatment quickly. We now have enough data to support the use of dopaminergic agents, benzodiazepines, antiepileptics, and opioids in these patients.

Humans↗

Bereitschaftspotential in idiopathic and symptomatic restless legs syndrome.

Patients with idiopathic and symptomatic restless legs syndrome (RLS) suffer from "dyskinesia while awake" or "daytime myoclonus" when at rest preceded by sensory symptoms. In order to characterise the RLS either as reflex movement or as voluntary movement we measured movement-related cortical potentials in 5 idiopathic and 8 uraemic RLS patients. Movements from both legs were polygraphically recorded concomitantly with cortical activity 2000 msec before to 500 msec after onset of EMG activity. These data were compared with a voluntary simulation of each patient's movement pattern and with 5 age-matched controls performing dorsiflexion of the right, left and both feet. Cortical activity preceding daytime myoclonus was absent in RLS patients whereas self-initiated leg movements in patients elicited onset times (1180-1380 msec) and amplitudes of Bereitschaftspotential (readiness potential) not significantly different from readiness potentials in control subjects (P > 0.05). Lack of movement-related potentials in myoclonus and/or dyskinesias during daytime in RLS patients is compatible with an involuntary mechanism of induction and points towards a subcortical or spinal origin of RLS.

Adult↗

Motor system excitability in patients with restless legs syndrome.

In 18 patients with idiopathic restless legs syndrome (RLS), intracortical inhibition by paired transcranial magnetic stimulation (TMS) was significantly reduced for both foot and hand muscles, suggesting that the entire motor cortex is disinhibited in RLS. Decreased intracortical facilitation in the foot muscle but not in the hand muscle may be due to subliminal activation of the symptomatic lower limbs. Motor excitability measurements of single TMS were not altered. These results support a subcortical origin of RLS.

Aged↗

MRI measurement of brain iron in patients with restless legs syndrome.

Brain iron insufficiency in the restless legs syndrome (RLS) has been suggested by a prior CSF study. Using a special MRI measurement (R2'), the authors assessed regional brain iron concentrations in 10 subjects (five with RLS, five controls). R2' was significantly decreased in the substantia nigra, and somewhat less significantly in the putamen, both in proportion to RLS severity. The results show the potential utility of this MRI measurement, and also indicate that brain iron insufficiency may occur in patients with RLS in some brain regions.

Aged↗

Investigation into the correlation between sensation and leg movement in restless legs syndrome.

We evaluated rest effects on restless legs syndrome (RLS) sensory and motor symptoms. During two 60-minute Suggested Immobilization Tests (SIT) subject's signals of RLS leg sensations and periodic leg movements while awake (PLMW) were recorded. Sensations, PLMW, sensations preceding or after PLMW, sensations occurring without following PLMW, and PLMW occurring without preceding sensation were determined. The RLS patients were divided into equal-sized high and low PLMW groups for further analysis. Data from 46 subjects (28 RLS and 18 controls) revealed sensations increased linearly with rest in RLS patients and controls. Movement rate increased linearly with rest for controls but increased rapidly for the first 45 minutes for all RLS patients. PLMW/hour increased with further rest for low but not high PLMW patients. Sensations followed by PLMW and PLMW without preceding sensations followed similar patterns. Sensations without subsequent PLMW increased dramatically in the last 15 minutes of the SITs. Whereas both sensory and motor signs of RLS increase with rest, there is minimal increase for controls. Patients with higher but not lower PLMW rates reached a ceiling for PLMW after 35 to 40 minutes. The temporal dissociation between sensory and motor events supports viewing these motor and sensory events as separate but loosely linked manifestations of RLS.

Aged↗

Bupropion may improve restless legs syndrome: a report of three cases.

Restless legs syndrome (RLS) is a common disorder for which agents that enhance dopaminergic activity, including dopamine agonists and levodopa, are the treatment of choice. However, long-term use of dopaminergic drugs can cause unwanted effects such as rebound, tolerance, and augmentation. Bupropion, an inhibitor of dopamine and noradrenalin reuptake, is an antidepressant that modulates dopaminergic systems. The authors report that a low dose of bupropion rapidly and completely ameliorated RLS symptoms in 3 depressed patients within a few days of the initiation of treatment. To their knowledge, this is the first report to show that bupropion may be an effective alternative for treating RLS. Consequently, bupropion may be useful for the treatment of patients with both depression and RLS.

Adult↗

Urinary 6-hydroxy-melatonin-sulfate excretion and circadian rhythm in patients with restless legs syndrome.

The precise etiology of the restless legs syndrome (RLS) is unknown. Sensory and motor symptoms of RLS worsen during evening/night, coincident with the physiological peak of pineal melatonin excretion. Decreased melatonin levels have been reported in insomnia, which is an associated feature of RLS. Melatonin substitution improved insomnia. A potential association between the idiopathic RLS (iRLS) and alterations in melatonin excretion was therefore explored. Daytime (7:00-22:00 hr) and night-time (22:00-7:00 hr) urinary excretion of 6-OH-melatonin-sulfate (aMLTs) was measured in 15 patients with iRLS and 11 controls by a radioimmunoassay. There was no significant difference between daytime and night-time urinary aMLTs excretion in iRLS as compared with controls (daytime: 6.14 +/- 5.20 ng versus 5.02 +/- 5.11 ng, NS; night-time: 21.07 +/- 17.05 ng versus 22.92 +/- 16.52 ng, NS). Our data do not provide evidence for a decrease of cumulative melatonin production in iRLS. Insomnia in RLS does not seem to be correlated with a deficit of melatonin.

Circadian Rhythm↗

Restless legs syndrome: an update on treatment options.

Restless legs syndrome (RLS) was first described in 1672 but it is only recently that this disorder has attracted attention in defining its phenotype, and identifying its aetiology, pathogenesis and pharmacological treatment. RLS can be divided into primary (idiopathic) and secondary forms. RLS is common, affecting 5-15% of the total population and manifesting at any age from childhood to late adulthood. Prevalence tends to increase with patient age and there may be geographic variation. There is a clear genetic contribution to primary RLS and evidence for dopaminergic dysfunction. Although not all patients with RLS require medication, there can be a substantial reduction in the patient's quality of life related to pain, poor sleep and excessive daytime sleepiness. A variety of medications are now available for the symptomatic treatment of RLS. Dopaminergic therapy is currently the treatment of choice, usually initiated with a long-acting dopamine agonist, thereby avoiding some of the complications associated with levodopa. Anticonvulsants may be used as second-line treatment. Levodopa should be reserved for those patients who fail to respond to alternative medications because of the high risk of inducing augmentation. Hypnosedatives also have a role in RLS management. Patients with intractable RLS may require combination treatment. Several systemic disorders can cause RLS, and these should be identified and treated appropriately.

Analgesics, Opioid↗

[Restless legs syndrome--current aspects].

Although the Restless-Legs-Syndrome (RLS) is harmless, it can be considerably bothersome on occasions. It seems to affect 1-5% of the population. The minimal criteria for diagnosis are: Symmetric or asymmetric dysesthesias of the lower, sometimes also of the upper extremities, present at rest, especially at night. This induces a need to move. Moving gives always relief, but only for a few seconds. Occasionally, dysesthesia can be painful. Additional features are: Involuntary, rhythmic retraction movements occurring especially at night, during sleep stages I und II. Sleep is disrupted and superficial, followed by daytime fatigue. Aetiologically, it is a mostly primary or hereditary disease, but may go along with uremia, diabetes and rheumatoid arthritis. Pathophysiologically there seems to be a malfunction of dopamine and opiate receptors in the central nervous system. Recently, morphological modifications have been found in peripheral nerves. Coffeine has been claimed as causative factor, but its role remains questionable. Therapy shows a high success rate. Some patients may complain about some remaining symptoms even with high doses of medication. Although carbamazepine, clonazepam and clonidine showed satisfactory results in controlled studies, dopaminergic agents and opiates have many advantages. In contrast to the former compounds, the latter are also effective against periodic movements in sleep. Side effects will be discussed according to the literature. In the second part of this paper, practical aspects concerning the care of RLS patients are considered.

Dopamine Agonists↗

EEG mapping in patients with restless legs syndrome as compared with normal controls.

Restless legs syndrome (RLS) is a sensorimotor movement and sleep disorder with a high prevalence. While the sleep disturbance due to RLS has been studied quite well polysomnographically, little is known about the electrophysiological function during daytime. The aim of the present study was to investigate the diurnal quantitative EEG and clinical symptomatology in 33 drug-free RLS patients as compared with age- and sex-matched normal controls. Investigations comprised brain mapping of the vigilance-controlled EEG as well as completion of the Zung Self-Rating Depression Scale, the Zung Self-Rating Anxiety Scale, the Quality of Life Index, the Pittsburgh Sleep Quality Index and the Epworth Sleepiness Scale for evaluation of clinical symptomatology. Statistical analysis demonstrated an increase in absolute delta and absolute and relative alpha-2 power, a decrease in absolute and relative alpha-1 power, an acceleration of the dominant frequency and the alpha centroid, and a slowing of the delta/theta centroid, as well as a non-significant attenuation in total power. These findings are characteristic of dissociated vigilance changes described in depression. Indeed, RLS patients demonstrated significantly higher depression and anxiety scores, lower quality of life and deteriorated sleep quality. The score of the Epworth Sleepiness Scale was not elevated, in contrast to the increased daytime sleepiness observed in other highly prevalent organic sleep disorders (e.g. sleep apnea). In conclusion, daytime EEG mapping revealed neurophysiological correlates of depression in RLS, which was confirmed by self-ratings at the symptomatological level.

Adult↗

Evaluating the quality of life of patients with restless legs syndrome.

BACKGROUND: The primary morbidities of restless legs syndrome (RLS) involve sleep loss, extreme discomfort, and disruption of normal activities. Although the condition is not life-threatening, assessing the disease burden and the impact of RLS on quality of life (QOL) is critical for evaluating treatment benefits. OBJECTIVE: The purpose of this study was to assess the impact of RLS on QOL. METHODS: In this subanalysis of a specific validation study, the SF-36 (Medical Outcomes Study 36-Item Short Form health survey) was administered to 85 patients with primary RLS who had been referred to a sleep-medicine clinic. The scores were compared with published norms for the general population (N = 2474). RESULTS: The majority (63.5%) of RLS patients were women; the mean (SD) age was 62.4 (14.0) years; 67.1% of patients experienced RLS symptoms almost daily. The RLS group, particularly patients with more severe RLS, reported significant deficits (10-40 points on 100-points scales) in physical functioning, bodily pain, role functioning, mental health, general health, and vitality compared with the general population. The RLS sample had significantly lower scores (worse QOL) on all 8 scales of the SF-36 compared with patients with hypertension (P<0.01); compared with patients with other cardiovascular conditions (ie, congestive heart failure, myocardial infarction within the past year, and angina), the RLS group had lower scores on 6 of the 8 scales. RLS patients had lower scores on 7 of 8 scales compared with diabetes patients, and on 4 of 8 scales compared with osteoarthritis patients. CONCLUSIONS: Comparison of the SF-36 scores of patients with RLS and the normative general population suggests that the disorder has a significant impact on patient QOL.

Adult↗

Exercise and restless legs syndrome: a randomized controlled trial.

BACKGROUND AND OBJECTIVES: Restless legs syndrome (RLS) is a common, underdiagnosed neurological movement disorder of undetermined etiology. The primary treatments for restless legs syndrome are pharmacological. To date, no randomized controlled trials have examined the effectiveness of an exercise program on the symptoms of RLS. METHODS: Study participants (N = 41) were randomized to either exercise or control groups. 28 participants (average age 53.7; 39% males) were available and willing to begin the 12-week trial. The exercise group was prescribed a conditioning program of aerobic and lower-body resistance training 3 days per week. Restless legs symptoms were assessed by the International RLS Study Group (IRLSSG) severity scale and an ordinal scale of RLS severity at the beginning of the trial, and at 3, 6, 9, and 12 weeks. RESULTS: Twenty-three participants completed the trial. At the end of the 12 weeks, the exercise group (N = 11) had a significant improvement in symptoms compared with the control group (N = 12) (P = .001 for the IRLSSG severity scale and P < .001 for the ordinal scale). CONCLUSIONS: The prescribed exercise program was effective in improving the symptoms of RLS.

Adult↗

[Pathophysiology of restless-legs syndrome. Review of current research].

The primary pathomechanism of restless legs syndrome is unclear. Neurophysiological, pharmacological, and imaging studies have demonstrated a complex interaction between central and peripheral structures. The degree of integration of central and peripheral mechanisms is not known. Altered excitability at a spinal level modulated by supraspinal rhythms of the brainstem possibly plays an important role. There is no anatomical structural lesion and it is more likely that circadian disturbances of dopaminergic and/or opioidergic neurotransmission are involved.

Adult↗

[Restless legs syndrome and periodic limb movements in sleep].

Restless legs syndrome is one of the most common neurological disorders, with a prevalence of 2% to 9% in the elderly population. Sensory and motor symptoms of the legs and an urge to move that occur at rest may lead to severe sleep disturbances and are part of the syndrome. Typical history and normal neurological examination lead to the clinical diagnosis. Additional laboratory and neurophysiological investigations are necessary to rule out associated diseases. The indication for polysomnography to record periodic limb movements in sleep must be discussed in individual cases. Treatment strategies will be recommended individually according to the disease severity. In this article we present an overview of the clinical symptomatology and include recommendations on diagnosis and treatment of RLS and differentiation of RLS from periodic limb movement disorder. To this purpose, the Motor System and Sleep Work Group of the German Society of Sleep Medicine presents modified guidelines for diagnosis and treatment of RLS according to recent recommendations of the American Sleep Disorder Association.

Aged↗

Restless legs syndrome and periodic movements of sleep.

Two entities of special interest in sleep disorders medicine are restless legs syndrome and periodic movements of sleep. Most patients with restless legs syndrome have periodic movements of sleep, but most patients with the nocturnal disorder do not have restless legs when awake. In both conditions, the underlying cause is obscure, and the frequency of occurrence increases with advancing age. In most patients with restless legs syndrome, the results of complete blood cell counts and iron, ferritin, folate, and vitamin B12 levels are normal. No hematologic or chemical abnormalities have been reported in patients with periodic movements of sleep who do not also have restless legs syndrome. Various pharmacologic agents, including benzodiazepines, opiates, and levodopa, have been proposed for the treatment of both disorders. Although some patients respond to a single drug for long periods, in many patients tolerance develops and the efficacy diminishes. In such circumstances, a reasonable approach is to alternate chemically unrelated agents on a weekly or biweekly schedule. Transcutaneous electric nerve stimulation may be beneficial.

Humans↗

Restless Legs Syndrome.

In the past 10 years, restless legs syndrome (RLS) has gained recognition as a common sleep disorder. There are several therapeutic options in treating patients with RLS. RLS causes significant sleep disturbance and negatively impacts on patient quality of life. Pharmacologic treatment can result in improved sleep and quality of life issues. RLS patients should be evaluated for iron deficiency anemia; iron replacement in deficient patients may lead to a resolution of symptoms or may reduce the severity of their symptoms. For patients with daily symptoms, the initial therapy is dopamine agonists. Low doses given in the evening or 2 hours before bed provide adequate relief of symptoms for many RLS patients. Augmentation can be seen with all dopamine agents, but is most prevalent with levodopa. Levodopa therapy is best used for milder intermittent symptoms or in aggravating situations, such as long car rides. Opiates and antiepileptics remain a beneficial therapy for RLS and are useful in patients who experience pain as part of their RLS. Newer anticonvulsants may provide additional treatment options, but they have yet to undergo clinical trials. Intravenous iron also may provide relief of RLS symptoms; however, dosing and safety issues have not been fully evaluated in a RLS population.

Journal Article↗

Restless legs syndrome: an update on diagnosis and management.

Restless legs syndrome (RLS) is a relatively common disorder that leads to considerable distress in and of itself and amplifies other physical symptoms, such as pain, by exacerbating sleep disturbance in affected patients. Due to its prevalence, it is important to query patients about this syndrome, evaluate for treatable causes, and provide palliative therapy to optimize comfort and normalize sleep patterns. This brief review summarizes current understanding of pathophysiology, epidemiology, differential diagnosis, and treatment modalities.

Aged↗