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PubMed1999

Secondary periodic limb movement disorder and restless legs syndrome.

Periodic limb movement disorder (PLMD) and restless legs syndrome (RLS) are well-known entities from a clinical and polysomnographic point of view. PLMD and RLS are seen mostly as primary or hereditary diseases, but may occur in conjunction to other diseases such as uremia, polyneuropathy, Parkinson's disease, and deficiencies of iron and magnesium. This review will discuss the prevalence, etiology and pathophysiology of secondary PLMD and RLS.

Journal Article↗
PubMed2000

Restless legs syndrome in 218 patients: associated disorders.

Background: Restless legs syndrome (RLS) is a disorder characterized by disagreeable sensations in the legs that occur at rest and are relieved by movement. These symptoms, which are worse at night, may result in sleep onset or sleep maintenance insomnia. Most patients are found on polysomnography (PSG) to have periodic limb movements in sleep (PLMS). The disorder, idiopathic in most cases, may be sometimes associated with specific disorders.Methods: Using the Province of Manitoba Health database, we compared the diagnoses made in the 5 years prior to sleep laboratory evaluation of 218 patients (103 men and 115 women) with RLS and 872 matched control subjects from the general population.Results: We found that 43.7% of male RLS patients vs. 10.4% of male controls and 46.1% of female RLS patients vs. 22.8% of female controls had been diagnosed as having psychological/psychiatric (most often depression) disorders (P<0.05). Extrapyramidal disease or movement disorders were previously diagnosed in 17.5% of male RLS patients vs. 0.2% of male controls and in 23.5% of female patients vs. 0.2% of female controls (P<0.05). Many patients had been previously diagnosed with disorders of the musculoskeletal system: 35.9% of male patients vs. 22.8% of male controls and 49.6% of female RLS patients vs. 23.3% of female controls had been diagnosed as having diseases of joints (male; P=ns, female; P<0.05). Disorders of the back were also more frequently diagnosed in RLS patients: 21.4% of male patients vs. 13.1% of male controls and 38.3% of female patients vs. 15.0% of female controls (male; P=ns, female; P<0.05).Conclusions: We conclude that RLS patients are much more likely to have previously been diagnosed with extrapyramidal disorders, musculoskeletal disorders, depression, and painful conditions such as joint and back disorders.

Journal Article↗
PubMed2005

Ropinirole in the treatment of restless legs syndrome.

Ropinirole is an original nonergoline dopamine agonist indicated for the treatment of Parkinson's disease. However, recent developments in the study of restless legs syndrome have demonstrated another role for this drug. The symptoms of restless legs syndrome are responsive to dopaminergic agents such as ropinirole. The dosage of ropinirole needed to treat the symptoms of restless legs syndrome appears to be much smaller than what is necessary for Parkinson's disease therapy. The liver is primarily responsible for the metabolism of ropinirole, which has an elimination half-life of approximately 6 h. Ropinirole is generally well tolerated, with no serious adverse effects. Clinical studies have indicated that ropinirole can effectively reduce the motor symptoms of restless legs syndrome and improve overall sleep quality.

Dopamine Agonists↗
PubMed1991

[No difference in efficacy of hydroquinine and placebo in restless legs syndrome].

OBJECTIVE: Determination of the efficacy of hydroquinine treatment of the restless legs syndrome. DESIGN: Double blind cross-over trial. SETTING: University Hospital Leiden. PATIENTS AND METHODS: Selection through an announcement in the press and followed by structured interview. Inclusion criteria according to the international classification of sleep disorders. Exclusion criteria defined by medication risks. Patients used either hydroquinine (200 mg in the evening and 200 mg before going to bed) or placebo in the second and fourth of four periods of two weeks duration. Severity of complaints was assessed using a daily questionnaire and a Suggested Immobilization Test (SIT) twice weekly, in which they noted the severity of complaints as experienced during a 15-minute period of immobilization. RESULTS: The study was completed by 59 out of 68 patients. Analysis of variance showed no significant differences between the two groups of patients (those starting with placebo and those starting with hydroquinine) for any of the questions of the daily questionnaire or of the SIT. McNemar's test showed no significant differences between the proportions of patients who wished to continue the use of either placebo or hydroquinine. CONCLUSION: This study showed no significant differences between the efficacy of placebo or hydroquinine in the restless legs syndrome.

Adult↗
PubMed2005

Restless legs syndrome: confirmation of linkage to chromosome 12q, genetic heterogeneity, and evidence of complexity.

BACKGROUND: Genes are involved in the etiology of restless legs syndrome, a common sensorimotor disorder. OBJECTIVES: To replicate and to further characterize our previously reported chromosome 12q linkage results. DESIGN: Family linkage study. SETTING AND PARTICIPANTS: A total of 276 individuals from 19 families have been examined using a selection of markers spanning the identified candidate interval on chromosome 12q. RESULTS: Two-point analyses of individual pedigrees indicated that 5 kindreds were consistent with linkage to chromosome 12q. When considering these 5 pedigrees along with the family in which linkage was originally reported, we observed a maximum 2-point logarithm-of-odds score of 5.67 (at theta = 0.10; for marker D12S1636; autosomal recessive) and a maximum multipoint logarithm-of-odds score of 8.84 between the interval defined by markers D12S326 and D12S304. Furthermore, our results also suggest the presence of heterogeneity in restless legs syndrome as linkage was formally excluded across the region in 6 pedigrees. Interestingly, significantly higher periodic leg movements during sleep indices were observed for all probands with restless legs syndrome from linked families. CONCLUSIONS: These results support the presence of a major restless legs syndrome-susceptibility locus on chromosome 12q, which has been designated as RLS1, and also suggest that at least one additional locus may be involved in the origin of this prevalent condition.

Chromosome Mapping↗
PubMed2004

Periodic limb movement disorder and restless legs syndrome in dialysis patients.

BACKGROUND: Sleep disturbances, in particular restless legs or limb movements, during the night are often reported by uremic patients. However, polysomnography (PSG) studies have never been carried out to confirm the actual occurrence of these disorders and the association with other objective and self-reported sleep-wake data. METHODS: Forty-eight participants were subjected to a 2-day PSG. These data on sleep including periodic limb movements, which are associated with restless legs, were correlated with clinical observations, quality of sleep-wake and life questionnaires, and with biochemical and neurographical measures. RESULTS: Restless legs syndrome (RLS) was observed in 58.3% of the patients and periodic limb movement disorder (PLMD) occurred in 70.8% of the patients. PLMD was revealed polysomnographically in almost 90% of the RLS patients. Patients with both PLMD and RLS had significantly poorer sleep quality than those with neither disorder or with PLMD alone, both in terms of self-reported data and the PSG. Quality of life was significantly worse in patients with RLS and PLMD compared to those patients with neither disorder. PLMD patients also tended to have a lower quality of life. All other metabolic measures and the results of a nerve conduction test were not correlated with RLS and/or PLMD. CONCLUSION: There was a high prevalence of severe RLS and PLMD in the present sample of uraemia patients. Nearly all RLS patients had severe PLMD. RLS (in combination with PLMD) in dialysis is associated with poor sleep quality, insomnia complaints, depression and emotional distress. Our results suggest that PLMD per se is also clinically relevant.

Female↗
PubMed1991

The role of the saphenous nerve in insomnia: a proposed etiology of restless legs syndrome.

Entrapment of the saphenous nerve after emergence from its lumbar roots and before its distribution to the medial surface of the leg is suggested as a cause of Restless Legs Syndrome (other anomalies of the saphenous nerve, especially those where the nerve is part of a general neuropathy, are not considered here). This finding is supported by evidence which: 1) identifies Restless Legs Syndrome as a nerve entrapment syndrome from: the dysesthesia in Meralgia Paresthetica, the paraesthesiae of Carpal Tunnel Syndrome and the poorly localized pain in pronator syndrome and suprascapular nerve entrapment; 2) isolates the saphenous nerve as the entrapped nerve from the patient's difficulty in identifying the precise area of sensation in saphenous nerve entrapment at Hunter's Canal; 3) localizes the pelvic region as the site of entrapment from rates of Restless Legs Syndrome of 11 and 19% in pregnant women, a correlation between chronic nonspecific prostatitis and Restless Legs Syndrome.

Female↗
PubMed2002

Increased CSF hypocretin-1 (orexin-A) in restless legs syndrome.

Hypocretin-1 levels were increased in evening CSF samples from subjects with restless legs syndrome, indicating altered hypocretin transmission in this sleep disorder. Increases in CSF hypocretin-1 levels were most striking in patients with early-onset restless legs syndrome.

Age of Onset↗
PubMed2004

Restless legs syndrome due to interferon-alpha.

A patient developed restless legs symptoms paralleling the course of interferon-alpha (IFN alpha) therapy for chronic hepatitis C. Symptoms began during a course of IFN alpha, resolved with its suspension, and recurred on rechallenge. Restless legs syndrome may thus be an adverse effect of IFN alpha treatment.

Antiviral Agents↗
PubMed1984

Clonazepam and vibration in restless legs syndrome.

There have been no controlled therapeutic trials in Restless Legs Syndrome (RLS). In 6 patients with RLS, a randomized double-blind cross-over trial vs placebo showed a significant efficacy of clonazepam in improving subjective quality of sleep and leg dysaesthesia. Vibratory stimulation of the leg showed a less pronounced and non-significant effect. Clonazepam is a safe and effective drug for treatment of RLS; however its long-term efficacy needs confirmation.

Adult↗
PubMed2001

[Restless legs syndrome].

The authors present recent data about epidemiology, pathogenesis and clinical features of idiopathic and symptomatic restless legs syndrome. A new aspects of pharmacological treatment and modification of daily activity are also described.

Diagnosis, Differential↗
PubMed2004

Restless legs syndrome and pregnancy.

OBJECTIVE: To perform a large and detailed epidemiologic study on restless legs syndrome (RLS) during pregnancy and the puerperium. METHODS: A structured clinical interview, assessing symptoms since the beginning of pregnancy, was performed to a population of 642 pregnant women at the time of delivery and at follow-up evaluation (1, 3, and 6 months after delivery). Main hematologic tests were also evaluated. A woman was considered affected if she met the International RLS Study Group criteria for RLS diagnosis. RESULTS: Twenty-six percent of women were affected by RLS during their pregnancy. The disease was strongly related to the third trimester of pregnancy and tended to disappear reaching the time of delivery. Affected women presented lower values of hemoglobin and mean corpuscular volume compared with healthy subjects (both groups received the same supplemental iron and folate therapy). CONCLUSIONS: Pregnancy is associated with transient restless legs syndrome.

Adult↗
PubMed2006

Less is more: pathophysiology of dopaminergic-therapy-related augmentation in restless legs syndrome.

Therapy-related augmentation of the symptoms of restless legs syndrome (RLS) is an important clinical problem reported in up to 60% of patients treated with levodopa and, to a lesser extent, with dopamine agonists. The efficacy of low-dose dopaminergic drugs for RLS has been established, but the mode of action is unknown. Here, we review the existing data and conclude that augmentation is a syndrome characterised by a severely increased dopamine concentration in the CNS; overstimulation of the dopamine D1 receptors compared with D2 receptors in the spinal cord may lead to D1-related pain and generate periodic limb movements; iron deficiency may be a main predisposing factor of augmentation, probably caused by a reduced function of the dopamine transporter; therapy with levodopa or dopamine agonists should remain at low doses and; iron supplementation and opiates are the therapy of choice to counter augmentation.

Circadian Rhythm↗
PubMed2005

Circadian variation of the effects of immobility on symptoms of restless legs syndrome.

STUDY OBJECTIVES: It is now well established that symptoms of restless legs syndrome (RLS) are worsened by immobility and that their severity fluctuates according to a circadian pattern with a maximum occurring in the late evening or during the night. However, no study has ever attempted to dissociate these two effects. The objective of this study was to evaluate the nycthemeral variations in the effects of duration of immobility on symptoms of RLS. DESIGN: A 28-hour modified constant routine protocol. SETTING: Sleep Disorders Center, Montreal Sacré-Coeur Hospital. PARTICIPANTS: Seven patients with primary RLS (3 men, 4 women; mean age: 43.9 years) and seven controls matched for age (42.4 years) and gender. INTERVENTION: None. MEASUREMENTS AND RESULTS: A 40-minute Suggested Immobilization Test (SIT) was repeated every 2 hours during the 28-hour protocol in order to quantify both subjective leg discomfort and periodic leg movements (PLM). Regarding leg discomfort, a two-way ANOVA performed on patients' data revealed a significant interaction (p = 0.037) between Time within the SIT and Time of day. Simple effect analyses performed to decompose the interaction showed that the increase in leg discomfort with duration of immobility was found only on SIT 7, 8, 9, 10 and 12, which corresponds to the period between 21:20 and 08:00. In addition, in patients, a significant circadian variation (p < 0.01) was found for the 28-hour profiles of leg discomfort progression during the SIT. No interaction or Time within the SIT effect was found for controls. CONCLUSIONS: These results show that worsening of RLS symptoms by immobility is closely linked to their intrinsic circadian variation.

Adult↗
PubMed1989

Understanding the pathogenesis of the restless legs syndrome at the level of the dopamine receptor. Are we about to identify the neurochemical deficiency causing schizophrenia?

According to a recent hypothesis, the restless legs syndrome is thought to be due to a caffeine-like substance produced by the human body (1). Some researchers have reported a case of familial restless legs that had high concentration of free dopamine in the cerebrospinal fluid (2). Other researchers have noticed the beneficial effect of opioids in the treatment of the restless legs syndrome (3). In this article, I am compiling information reconciling the findings of those researchers with the hypothesis that proposes that the restless legs syndrome is due to a caffeine-like substance produced by the human body. Also, I am addressing the pathogenesis of the restless legs syndrome at the level of the dopamine receptors in the central nervous system. Understanding this pathogenesis probably will help in identifying the neurochemical deficiency causing schizophrenia.

Brain↗
PubMed1996

Restless legs syndrome: clinicoetiologic correlates.

Despite recent attempts to better characterize restless legs syndrome (RLS), this neurologic disorder remains poorly understood. The relationship between idiopathic and secondary and between familial and sporadic (nonfamilial) cases have not been previously defined. We studied 54 patients (29 women and 25 men) who satisfied the diagnostic criteria for RLS. The mean age of the patients was 62.69 +/- 13.82 years, and the mean age at onset was 34.13 +/- 20.30 years. We found that 92% of patients with idiopathic RLS (without neuropathy) had a family history of RLS, whereas only 13% of those with neuropathic RLS (associated with peripheral neuropathy) had a positive family history. The sporadic/neuropathic patients were older at symptom onset and tended to have a more rapid progression than the familial/idiopathic patients. There were no other significant differences between the subgroups. Levodopa and dopamine agonists were the most effective treatments. We conclude that there are two major etiologic subgroups of RLS but that the two share central pathophysiologic mechanisms.

Adult↗