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PubMed2001

Treatment of idiopathic restless legs syndrome (RLS) with gabapentin.

Nine patients with idiopathic restless legs syndrome (RLS) were treated with 300 mg of gabapentin as an initial dose and an up-titration until relief of symptoms for 4 weeks. Subjective symptoms improved significantly. Polysomnographic data showed a reduction of periodic leg movements during sleep (PLMS) (p = 0.003) and PLMS index (p = 0.001). The authors conclude that gabapentin provides a well-tolerated and effective treatment of idiopathic RLS.

Acetates↗

PubMed1999

Circadian rhythm of motor restlessness and sensory symptoms in the idiopathic restless legs syndrome.

STUDY OBJECTIVES: To determine if motor restlessness in the Restless Legs Syndrome (RLS) shows a circadian rhythm with maximum at night, as previously found for subjective discomfort and periodic limb movements (PLMs), and to correlate RLS peak intensity with the core temperature cycle. DESIGN: Subjects underwent two days of normally timed wakefulness and sleep followed by a night and subsequent day of sleep deprivation. Activity was standardized through modified suggested immobilization tests (mSITs). SETTING: The study was conducted in a laboratory environment with a bedroom equipped for polysomnography during sleep and the mSITs. PATIENTS: Nine patients (mean age 59.8+/-11.3 years [range: 33-72]; 4 males, 5 females) with clinically severe idiopathic RLS. INTERVENTIONS: Patients were monitored with continuous ambulatory activity and core temperature recording. The mSITs were performed every three hours while subjects were awake. During the mSITs, subjective discomfort was measured every 15 minutes while motor restlessness was assessed through activity monitoring. MEASUREMENTS AND RESULTS: Subjective discomfort and motor restlessness increased from a trough in the morning to a maximum at night in the hours following midnight. Peak intensity was found on the falling phase of the core temperature cycle, whose circadian rhythm appeared to be within the normal range for age. CONCLUSIONS: An independent circadian factor modulates the intensity of RLS, which seems to peak on the falling phase of the core temperature cycle. Therefore, the diagnostic criteria that RLS occurs with rest and during the night have independent bases. Furthermore, RLS may be partially controlled by some process or substance whose level varies with the normal circadian rhythm.

Adult↗

PubMed2005

Restless legs syndrome.

PURPOSE OF REVIEW: In the review period since February 2004 a number of papers have been published that make significant contributions to the current understanding of the epidemiology, clinical assessment, pathophysiology and treatment of restless legs syndrome. Those with the most significant findings were selected and will be reviewed. RECENT FINDINGS: Several epidemiological studies about restless legs syndrome have become available in the review period. A new susceptibility locus for restless legs syndrome has been reported. Neuropathological studies have provided profound insights into the key role of iron regulation in the pathophysiology of restless legs syndrome. Several randomized, double-blind, placebo-controlled studies have demonstrated that dopamine agonists are efficacious in the treatment of restless legs syndrome. A few pilot treatment studies with intravenous iron have been performed. SUMMARY: In this paper, recent advances in the field of restless legs syndrome are reviewed. Special emphasis is placed on pathophysiology and treatment. Restless legs syndrome is still an underdiagnosed disorder. The evidence basis for its treatment has been considerably increased in the review period.

Anticonvulsants↗

PubMed2002

Subjective sleep quality and suggested immobilization test in restless leg syndrome and periodic limb movement disorder.

The severity of restless leg syndrome (RLS) and/or periodic limb movement disorder (PLMD) was investigated by using a suggested immobilization test (SIT) and by measuring the influence of these disorders on the subjective sleep quality as assessed by the Pittsburgh Sleep Quality Index (PSQI). Patients with RLS and those with both RLS and PLMD showed remarkably high values for PSQI and SIT, whereas patients with PLMD only showed normal values for PSQI. These findings suggest that there is only a small pathological significance for periodic limb movements, and demonstrate the efficacy of SIT and PSQI for evaluating the severity of these disorders.

Electromyography↗

PubMed2006

Restless legs syndrome and periodic limb movements.

The history, clinical aspects, and treatment of restless legs syndrome (RLS), a heterogeneous distressing sensorimotor disorder, and periodic limb movements (PLMs) that are the typical motor accompaniment of the syndrome, are described. A positive family history, a positive response to dopaminergic treatment, and the presence of PLM while awake or asleep are supportive criteria for the diagnosis of the disorder. RLS and PLM occur more frequently at the beginning of night and exponentially decline across sleep cycles, suggesting circadian influences. Altered circadian rhythmicity in dopamine metabolism and enhanced circadian variations in dopaminergic functions have been reported in the disorder. Dysfunction or atrophy of A11 cells from the diencephalic-spinal dopamine A11 system has been suggested to explain the efficacy of dopaminergic drugs in relieving RLS symptoms and the circadian rhythmicity of RLS. Studies support the hypothesis that the A11 dopaminergic neurons and spinal pathways may be more involved in the pathophysiology of RLS than the nigrostriatal system. Neurophysiological evidence indicates that the involuntary movements in RLS may be of spinal or propriospinal origin. Despite these findings, however, the pathogenic mechanisms underlying the peculiar sensory and motor manifestations of RLS remain unexplained. Among the current treatment options offered for the treatment of RLS, dopaminergic agents have provided the best evidence for efficacy in symptom relief.

Circadian Rhythm↗

PubMed2001

Restless legs syndrome: a clinical study of 55 patients.

BACKGROUND: Restless legs syndrome (RLS) is a common sleep disorder. In 1995, clinical criteria for the diagnosis of RLS were defined. OBJECTIVE: To describe the clinical spectrum in a series of unselected RLS patients meeting the new diagnostic criteria. METHODS: We prospectively assessed by questionnaire and clinical assessment the characteristics of 55 consecutive RLS patients (35 women, 20 men; mean age = 62 +/- 16 years). RESULTS: In 27% of the patients, RLS started before the age of 20 years (early-onset RLS). Sensory disturbances were painful in 56% of patients and felt in legs (98%), arms (35%), and 'internally' (45%). Motor disturbances included 'dyskinesias while awake' (36%). Insomnia (58%) was commoner than hypersomnia (24%). In 67% of the patients, no etiology of RLS was found (idiopathic RLS). Early-onset RLS was more commonly familial (p = 0.01) and associated with 'growing pains' (p = 0.005) than late-onset RLS. Patients with RLS and hypersomnia were younger (p = 0.01) and less commonly had painful sensations (p = 0.04) than patients with RLS and insomnia. Patients with idiopathic RLS were younger (p = 0.004), and less commonly had insomnia (p = 0.01) than patients with symptomatic RLS. CONCLUSIONS: RLS is a clinically pleomorphic syndrome, reflecting the contribution of multiple genetic and acquired factors in the pathogenesis of RLS.

Adult↗

PubMed1996

Periodic limb movements of sleep and the restless legs syndrome.

Periodic limb movements of sleep and the restless legs syndrome are not diagnoses but rather an indication that there is some CNS disturbance and are associated with an ever-growing number of conditions. They are very common, exist in many forms and are often overlooked by physicians. It is the author's opinion that they are parts of what has been called an akathisia syndrome in the most severe situations and may include the same mechanisms that underlie attention disorders, chronic fatigue syndrome and "sun-downing." They are likely parts of a syndrome caused by dysfunction in a complex brainstem center. This center's normal function is to maintain a smooth electrical template on which discrete neuronal impulses sculpture the rich repertoire we recognize as sensory and motor function awake and to effect a smooth "switching" mechanism allowing sleep to occur without motor and sensory input invading consciousness (awakening). While the DA-ergic CNS pathways have been thought to be the primary neurotransmitter involved, the opioids secondary, there is mounting evidence that the situation is far more complicated, that many neurotransmitter, including stimulating and inhibiting amino acids, play a part. These patients agonize with their indisposition but can be helped by various treatments. Treatment alleviates not only the distress caused by the symptoms but also the devastating insomnia and excessive daytime sleepiness associated with it.

Acetates↗

PubMed2001

Piribedil for restless legs syndrome: a pilot study.

Thirteen consecutive patients with restless legs syndrome (RLS) were treated with piribedil and were rated using an RLS rating scale (0-10) and subjective response (0-100%); 11/13 (85%) had improvement of their mean RLS scores with subjective response ranging from 30% to 100% (mean 74.6%). This pilot study suggests that piribedil is effective for RLS.

Adult↗

PubMed1990

Restless legs syndrome and nocturnal myoclonus: initial clinical manifestation of familial amyloid polyneuropathy.

Restless legs syndrome was the first isolated clinical manifestation in four siblings of a family with familial amyloid polyneuropathy. Clinical and electrophysiological evidence of peripheral neuropathy appeared after a variable time interval. Polysomnography showed abnormal sleep patterns and nocturnal myoclonus in all patients. The restless legs syndrome responded favourably to clonazepam.

Aged↗

PubMed1997

Pergolide in the management of restless legs syndrome: an extended study.

Twenty patients with problematic restless legs syndrome (RLS) were treated with pergolide. Efficacy, dosage, side effects, and tolerance were analyzed. Fifteen patients continued treatment for a median study time of 2 years. Five patients discontinued treatment after a mean of 4.2 months. Pergolide resulted in complete or near complete control of symptoms in 45% and moderate control in 50% of patients studied. Levodopa-induced daytime augmentation resolved in all patients in whom it had been present. The mean total daily maintenance dose of pergolide was 0.23 mg. Forty percent required an additional afternoon dose. Side effects developed in 12 patients (60%) and necessitated discontinuation of treatment in five. Common side effects were nausea, dizziness, and insomnia. Daytime augmentation occurred in 27% of patients, but this was mild and usually easily controlled with a supplementary afternoon dose of pergolide. Tolerance did not develop. We conclude that pergolide is an effective second-line agent for RLS, especially following levodopa-induced daytime augmentation.

Adult↗

PubMed2002

Restless legs syndrome: a sensorimotor disorder of sleep/wake motor regulation.

Restless legs syndrome (RLS) remains an underappreciated sensorimotor disorder of sleep/wake regulation. It is one of the few sensorimotor disorders that is provoked by rest and that also follows a clear circadian pattern. Recent epidemiologic studies have verified that the condition is common in populations derived from the north and west of Europe, and have begun to uncover some of the genetic substrate of the disorder. New instruments have been developed to facilitate diagnosis and assessment of severity. The pathogenesis of the condition remains uncertain, but recent discoveries implicate areas of the nervous system from the spinal cord up to the basal ganglia. A current hypothesis undergoing vigorous exploration is that the condition results from a deficiency of dopaminergic function based on abnormalities of iron transport and storage. Therapeutically, studies have shown the dopamine agonists to be the most reliable treatment for severe cases, whereas other recent studies have successfully utilized a number of other medications, including levodopa, opioids, and anticonvulsants. New standards provide guidelines for management of RLS and make specific pharmacotherapeutic recommendations.

Humans↗

PubMedDate not supplied

High-dose clonidine in a case of restless legs syndrome.

OBJECTIVE: To describe a patient with idiopathic restless legs syndrome (RLS). CASE SUMMARY: A 37-year-old man developed severe symptoms of RLS. Treatment using combinations of levodopa, opioids, benzodiazepines, and baclofen provided only partial benefit or resulted in intolerable adverse effects. Higher dosages of clonidine than previously reported in the literature (0.9 mg/d in divided doses) were needed to completely relieve his RLS symptoms. The only prominent adverse effect was dry mouth. The RLS symptoms returned after subsequent reductions in the dosage. After the dosage of clonidine was again increased, complete relief of the symptoms was achieved again. After several months, clonidine was tapered to zero and the patient entered a period of spontaneous remission. When his symptoms returned four months after clonidine had been discontinued, clonidine therapy was restarted. DISCUSSION: Clonidine alleviated RLS symptoms in 30 of 41 patients reported in the literature, indicating that the adrenergic nervous system may play a role in RLS. CONCLUSIONS: High-dose clonidine appears to be useful in treating RLS when other therapies fail. However, well-controlled, polysomnographic studies are needed.

Adult↗

PubMed2005

Secondary causes of restless legs syndrome in older people.

BACKGROUND: Secondary causes of restless legs syndrome (RLS) have been reported to be more common in those with late-onset RLS. However, 'late-onset' in previous studies was defined as onset after 45 years. OBJECTIVE: To determine the prevalence of secondary causes of RLS and the relationship between aetiological factors and age of symptom onset in an older population. DESIGN: Prospective study conducted over a 5-year period. PARTICIPANTS: 80 consecutive non-related patients diagnosed with RLS. MEASUREMENTS: Patients were assessed according to a standard protocol. Age at symptom onset, severity of symptoms, neurological findings and laboratory tests were examined. RESULTS: Iron deficiency (serum ferritin <50 ng/ml) was present in 22% of patients with onset before 50 years, 39% of those with onset at 50 to 64 years and 58% in those with onset after 64 years (P = 0.009). Clinical neuropathy was also more common in older-onset patients (P = 0.08). Family history was positive in 39%, 23% and 8% of these groups, respectively (P = 0.008). CONCLUSION: Secondary causes of RLS become more common and a positive family history less common with increased age of symptom onset.

Adult↗

PubMed2004

Correlation of anxiety and depression symptoms in patients with restless legs syndrome: a population based survey.

BACKGROUND AND OBJECTIVES: Restless legs syndrome (RLS) is an important and common cause of insomnia, and previous studies indicate that psychiatric wellbeing may be impaired among RLS patients. We aimed to investigate the interaction between anxiety/depression and RLS in a population based survey. METHODS: Data were drawn from the Mersin University Neuro-Epidemiology Project, a representative community sample of adults aged over 17 years residing in Mersin (n = 3234). Subjects found to be positive for RLS (n = 103) were evaluated for symptoms of anxiety and depression using the Hamilton Anxiety and Depression Scales and compared with the same number of contemporaneous control subjects. RESULTS: Significantly greater anxiety and depression symptoms were observed among patients with RLS than in the control subjects. Our data also seem to provide initial evidence of a correlation between the severity of RLS and of anxiety and depression symptoms (r = 0.21, p = 0.03 and r = 0.201, p = 0.04 respectively). CONCLUSIONS: Assessment of psychiatric status of RLS patients can be helpful and sometimes necessary to determine additional features and treatment strategies of this bothering condition. Further studies are needed to replicate our findings using longitudinal data.

Adolescent↗

PubMed2003

Neuropathological examination suggests impaired brain iron acquisition in restless legs syndrome.

OBJECTIVE: To assess neuropathology in individuals with restless legs syndrome (RLS). METHODS: A standard neuropathologic evaluation was performed on seven brains from individuals who had been diagnosed with RLS. The substantia nigra was examined in greater detail for iron staining and with immunohistochemistry for tyrosine hydroxylase and proteins involved in iron management. Five age-matched individuals with no neurologic history served as controls. RESULTS: There were no histopathologic abnormalities unique to the RLS brains. Tyrosine hydroxylase staining in the major dopaminergic regions appeared normal in the RLS brains. Iron staining and H-ferritin staining was markedly decreased in the RLS substantia nigra. Although H-ferritin was minimally detected in the RLS brain, L-ferritin staining was strong. However, the cells staining for L-ferritin in RLS brains were morphologically distinct from those in the control brains. Transferrin receptor staining on neuromelanin-containing cells was decreased in the RLS brains compared to normal, whereas transferrin staining in these cells was increased. CONCLUSIONS: RLS may not be rooted in pathologies associated with traditional neurodegenerative processes but may be a functional disorder resulting from impaired iron acquisition by the neuromelanin cells in RLS. The underlying mechanism may be a defect in regulation of the transferrin receptors.

Aged↗

PubMed2006

Absence of postexercise and delayed facilitation of motor cortex excitability in restless legs syndrome: evidence of altered cortical plasticity?

STUDY OBJECTIVE: Restless legs syndrome (RLS) is a neurologic disorder with well-defined clinical and diagnostic criteria but the pathophysiology of which is unclear. Previous studies have suggested alterations in motor cortex function in RLS. We aimed to compare motor cortex plasticity in subjects with RLS versus healthy controls. DESIGN: Biphasic single-pulse transcranial magnetic stimulation (TMS) of the nondominant hemisphere was used to define motor evoked potential (MEP) amplitude, motor threshold, and silent period. Subjects also performed 3 blocks (30-s, 60-s, and 90-s duration) of a bimanual motor task (exercise condition). Amplitude of MEPs elicited immediately after each block, and then after a 15-minute rest period were compared with baseline. The time course of intracortical inhibition was also tested using paired-pulse TMS at 1- to 6-millisecond interstimulus intervals. SETTING: Clinical neurophysiology laboratory in a General Hospital. STUDY PARTICIPANTS: For the single-pulse TMS procedures, the RLS group included 11 patients affected by primary RLS and the control group included 11 age- and sex-matched normal subjects. For the paired-pulse TMS procedures, there were 9 patients and 6 controls. INTERVENTIONS: None. RESULTS: There were no group differences in motor threshold and MEP amplitudes, but the silent period was significantly shorter in subjects with RLS. Compared with baseline, control subjects had larger MEP amplitudes after 30 and 60 seconds of exercise and also after the rest period. In contrast, MEP amplitudes in patients with RLS were not significantly different from baseline after any of the exercise conditions or following the rest period. Patients with RLS also had decreased short-latency paired-pulse inhibition. CONCLUSIONS: Findings show abnormal motor cortex inhibition and cortical excitability differences in RLS. We suggest the possibility of alterations in movement-related cortical plasticity in RLS.

Arousal↗

PubMed2005

Pediatric sleep-related breathing disorders and restless legs syndrome: how children are different.

Sleep-related breathing disorders and restless legs syndrome have traditionally been felt to affect primarily adults. Recent research suggests that these conditions are surprisingly common in children as well, and that clinical manifestations may differ considerably from those seen in adults. This review summarizes the clinical characteristics, epidemiology, pathophysiology, and treatment of sleep-related breathing disorders and restless legs syndrome in children. Particular emphasis is placed on recent research and on how the presentation and treatment of these conditions are different in children compared with adults.

Adolescent↗

PubMed2005

[Comparison of therapeutic effects of acupoints selected along different meridians on restless legs syndrome].

OBJECTIVE: To compare therapeutic effects of different acupoints selected on restless legs syndrome. METHODS: Eighty-one cases were randomly divided into a treatment group (n=41) treated by acupoint selection method according to nerve anatomy and combination of positive findings with neurobiological theory, and a control group (n=40) treated by traditional acupoint selection method. RESULTS: The effective rate and the markedly effective rate were 97.6% and 90.3% in the treatment group, and 75.0% and 60.0% in the control group with significant differences between the two groups (P < 0.01), and there was a significant difference between the two groups in the needed treatment times for the cured cases (P < 0.01). CONCLUSION: The acupoint selection method according to nerve anatomy, positive findings and neurobiological theory has a better therapeutic effect on restless legs syndrome as compared with the traditional method.

Acupuncture Points↗