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PubMed2004

Analysis of familial and sporadic restless legs syndrome in age of onset, gender, and severity features.

Restless Legs Syndrome is characterized by the irresistible, often indescribable unpleasant urge to move the limbs while resting. It has an estimated prevalence of approximately 29.3 % in US private practice. Restless Legs Syndrome often has a familial component; whether the familial and non-familial forms differ in terms of clinical features has previously been investigated, with the only significant factor emerging as younger age at onset in familial cases. Our study further explores a possible underlying difference between familial and sporadic forms of RLS by comparing familial RLS with sporadic RLS in terms of demographic and clinical features including subject gender, age of onset, and severity measures based an the IRLSSG severity scale. Both gender and family history are significant predictors of onset age in an overall model and also significant when analyzed independently. Participants who reported more severe RLS symptoms were significantly younger in age and progressed more rapidly. Two variables from the IRLSSG severity scale were significantly associated with age of onset when tested independently: discomfort and the urge to move the limb for relief. Our analysis supports the prevailing hypothesis that RLS is divided into earlier onset disease with a clear genetic component and later onset disease with unclear etiology, and that one or more endophenotypes might exist within the disorder which could further characterize these subjects for future genetic studies.

Age of Onset↗

PubMed1990

Variable expressivity in familial restless legs syndrome.

A 62-year-old man with a 20-year history of excessive daytime somnolence and kicking during sleep was an obligate carrier of the restless legs syndrome gene because his paternal grandfather, father, and all three of his children had symptoms of restless legs syndrome. The patient himself, however, denied motor restlessness after a careful and exhaustive medical history and he was originally believed to have periodic movements in sleep without restless legs. Close clinical observation did reveal nighttime motor restlessness, although the patient continued to deny its importance. Polysomnography showed frequent periodic movements in sleep. We conclude that there can be variable expressivity of the clinical features in familial restless legs syndrome and that there are probably some relatively nonrestless patients with prominent periodic movements in sleep who are carriers of the restless legs syndrome gene. Some sleep-disordered patients who are believed to have only periodic movements in sleep may have a forme fruste of autosomal dominant restless legs syndrome. If one does not examine these patients carefully at night and take an adequate family history, one may miss the diagnosis of restless legs syndrome.

Gene Expression↗

PubMedDate not supplied

Validation of the Restless Legs Syndrome Quality of Life questionnaire.

OBJECTIVES: The Restless Legs Syndrome Quality of Life questionnaire (RLSQoL) assesses the impact of RLS on daily life, emotional well-being, social life, and work life. This study investigates its validity and reliability. METHODS: The RLSQoL was tested in 85 American adults with primary RLS. Patients were also asked to rate symptom severity with the International Restless Legs Scale (patient-reported version) and report on changes in symptoms over the 2-week period. RESULTS: The RLSQoL summary scale score (range: 0-100) demonstrated acceptable internal consistency reliability (Cronbach's alpha = 0.92) and test-retest reliability (intraclass correlation coefficient = 0.84). All items indicated acceptable item-convergent validity. The RLSQoL distinguished between groups with mild, moderate, and severe symptoms (F = 52.22, P < 0.0001). It demonstrated preliminary responsiveness to changes in RLS status over 2 weeks (effect size: improvement, 0.25; deterioration, -0.32), indicating moderate scale changes consistent with the small clinical change over this time. CONCLUSIONS: These findings support the conceptual framework of the RLSQoL. It is a valid and reliable measure of the impact of RLS on QoL and is responsive to short-term changes in symptom severity. The RLSQoL appears to be an appropriate tool for trial-based assessments of treatments for RLS.

Adult↗

PubMed2007

A better future for patients with restless legs syndrome.

Despite advances in the management of restless legs syndrome (RLS), there still is a great deal of uncertainty about its etiology, pathophysiology, therapy, and clinical outcomes. Much remains to be learned. Future research on these issues will help identify the optimum therapeutic approach for the diverse group of patients with RLS.

Clinical Trials as Topic↗

PubMed2006

Medication tolerance and augmentation in restless legs syndrome: the need for drug class rotation.

Restless legs syndrome (RLS) is a common condition characterized by an unpleasant urge to move the legs that usually occurs at night and may interfere with sleep. The medications used most commonly to treat RLS include dopaminergic drugs (levodopa, dopamine agonists), benzodiazepines, and narcotic analgesics. We report the cases of 2 patients with RLS who illustrate the problems of tolerance (declining response over time) and augmentation (a worsening of symptoms due to ongoing treatment) that can complicate the pharmacotherapy of RLS. We discuss the optimal management of RLS and propose strategies to overcome tolerance and augmentation such as a rotational approach among agents from different classes.

Aged↗

PubMed2000

Periodic arm movements in patients with the restless legs syndrome.

A high proportion of patients with restless legs syndrome (RLS) also complain of arm paresthesia but the presence of periodic arm movements (PAM) has never been documented in a sleep laboratory in these patients. We investigated the prevalence of PAM during nocturnal sleep and awakenings in 22 RLS patients. Fifteen patients had a PAM index >5 movements per hour during wakefulness and among them only 3 had a PAM index >5 during sleep. Twenty patients had a periodic leg movement (PLM) index >5 during wakefulness and 17 had a PLM index >5 during sleep. In 42.8% of cases, PAM showed temporal relationship with PLM during wakefulness. These results show that PAM is frequent in RLS and suggest that the basic neurological dysfunction responsible for RLS is probably not located exclusively at the level of the lumbar spinal cord but involves neuronal systems located at upper levels.

Adult↗

PubMed2000

Pramipexole in the treatment of restless legs syndrome: a follow-up study.

The restless legs syndrome (RLS) is a condition characterized by unpleasant limb sensations occurring at rest and associated with an irresistible urge to move. Several treatments are used to treat RLS including benzodiazepines, opioids, dopaminergic agents, clonidine and anticonvulsant drugs such as carbamazepine and gabapentine. Dopaminergic agents are now considered the treatment of choice for RLS. Levodopa is effective in treating RLS; however, several patients treated with levodopa at bedtime developed morning or late afternoon restlessness. Recently, more attention has been paid to dopamine receptor agonists. Ergoline derivatives, bromocriptine and pergolide were found effective, but require concomitant administration of domperidone, a peripheral dopamine antagonist. In a recent study, we studied the efficacy and innocuity of pramipexole, a new dopamine agonist with a higher affinity for the D3 receptor subtype of the D2 family, in a double-blind, placebo-controlled, randomized trial. Pramipexole had major effects on RLS symptoms without severe side-effects. The present study aimed to assess the long-term efficacy of pramipexole. Seven patients were treated with the drug for a mean follow-up duration of 7.8 months. Treatment was started at a dosage of 0.25 mg, and progressively increased until the optimal therapeutic effect was obtained. Home questionnaires were completed for 7 consecutive days, after one month and after a mean of 7.8 months of treatment with pramipexole, assessing leg restlessness during the daytime, in the evening, at bedtime and during the night. There was no evidence of a decrease in the therapeutic effect of pramipexole in these patients, even 7.8 months after the initiation of treatment. The optimal dosage was 0.25 mg for one patient, 0.5 mg for five patients and 0.75 mg for one patient. While there was a progressive increase in severity of leg restlessness from daytime to nighttime before treatment, a suppression of leg restlessness was observed throughout the 24 h with a single dose of pramipexole at bedtime. The remarkable efficacy of pramipexole raises the possibility that the D3 receptors of the mesolimbic system may be more specifically involved in the physiopathology of RLS.

Adult↗

PubMed2003

Multiple blood donations associated with iron deficiency in patients with restless legs syndrome.

OBJECTIVE: To describe a series of patients with restless legs syndrome (RLS) and iron deficiency with and without anemia related to repeated blood donations. PATIENTS AND METHODS: Study patients were identified by asking consecutive patients with RLS seen at the Mayo Clinic in Rochester, Minn, from February 1 to December 31, 2001, whether they donated blood. All patients who fulfilled the International Restless Legs Syndrome Study Group criteria for RLS, had donated blood a minimum of 3 times a year the preceding 3 years, and had iron deficiency (serum ferritin concentration <20 microg/L) were included in the study. RESULTS: Eight patients met the study criteria. The mean +/- SD serum ferritin concentration was 8.1 +/- 3.5 microg/L, and 4 patients had anemia. In 6 of the 8 patients, RLS began at about the same time of or after blood donation. Patients had donated blood for 4.2 +/- 13 times a year (range, 3-6 times a year) for 15.2 +/- 83 years (range, 5-25 years). Hemoglobin concentrations were 12.8 +/- 1.8 g/dL (range, 10.6-15.5 g/dL). In 2 patients, RLS essentially resolved with correction of iron stores alone, and medications for RLS were successfully discontinued in 2 other patients. CONCLUSIONS: Repeated blood donation is associated with induction or perpetuation of RLS due to iron deficiency with or without coexisting anemia. Potential blood donors should be questioned about RLS, and donation should not be allowed until the serum ferritin concentration has been measured and iron stores replenished if necessary.

Adult↗

PubMed1991

Review and videotape recognition of idiopathic restless legs syndrome.

The motor phenomena associated with idiopathic restless legs syndrome (RLS) are infrequently seen in the physician's office because they are present only after prolonged sitting or lying and usually at night. These motor phenomena are captured on videotape in four unrelated patients with idiopathic RLS. The clinical features of idiopathic RLS are reviewed in detail, and therapeutic advances in its treatment are summarized.

Anti-Anxiety Agents↗

PubMed2006

CAG repeats in Restless Legs syndrome.

Recent reports established an association of restless legs syndrome (RLS) and spinocerebellar ataxia (SCA) type 1, 2, and 3. To evaluate the contribution of SCA alleles to idiopathic RLS we investigated the CAG repeat length at the SCA1, SCA2, SCA3, SCA6, SCA7, and SCA17 loci in 215 patients who fulfilled the clinical criteria of RLS and presented periodic leg movements in sleep (PLMS) in polysomnographic recording. Fifty percent of patients had a positive family history of RLS. We found one intermediate (CAG)(43) allele for SCA17 in a 44-year-old female with RLS starting at the age of 43. Neurologic examination and family history were unremarkable in this patient. Otherwise, allele distribution did not differ between RLS patients and healthy controls. Stratification for age, age of onset, sex, peripheral neuropathy, and sporadic or familial RLS revealed no effect. Thus, CAG repeat length in the investigated genes is not a major determinant of idiopathic or familial RLS.

Adult↗

PubMedDate not supplied

Restless legs syndrome--relevant aspects for internal medicine specialists.

Restless legs syndrome (RLS), also known as Ekbom's syndrome, is a fairly common complaint which is not widely recognised by medical professionals, although it seems to affect 1-10% of the population. Despite recent attempts to better characterize RLS, this neurologic disorder remains poorly understood. Idiopathic RLS frequently follows an autosomal dominant inheritance with a variable clinical expressivity of symptoms. Secondary RLS is usually associated with neuropathy of chronic disorders (uremia, cryoglobulinemia, diabetes mellitus, infections, etc). RLS gives the sufferer an unpleasant sensation in the legs at rest, causing an irresistible desire to move which alleviates the discomfort. Other features that characterize RLS include sleep disturbance, involuntary movements in sleep or wakefulness, a normal neurologic examination, a chronic clinical course (waxing and waning over the time), and, in some cases, a positive family history. Periodic limb movements during sleep, which also may occur as an isolated finding, may or may not cause frequent arousals or awakenings. Clinical diagnosis of idiopathic or symptomatic forms of RLS can be supported with polysomnography. Full understanding of the features of RLS will provide the clinician with the strongest tool for recognizing the disorder. Many different treatments have been tried for RLS. Since the cause is unclear, therapy of RLS and PLMS remains symptomatic except for some secondary forms. Treatment of first choice consists of dopaminergic drugs or dopamine agonist, opioids and benzodiazepines.

Aged↗

PubMedDate not supplied

Nocturnal myoclonus in restless legs syndrome effect of carbamazepine treatment.

We studied Restless Legs Syndrome (RLS) and nocturnal myoclonus (NM) in 9 patients before and after carbamazepine treatment, to verify the correlation between improvement of RLS and modification of NM pattern during sleep. Although CBZ proved effective in the treatment of RLS, it did not modify the pattern of nocturnal myoclonus and its relationship to arousal during sleep. The efficacy of CBZ on RLS may be due to other properties of the drug rather than to the effect on nocturnal sleep: reduction of sleep latency and wakefulness after sleep onset.

Adult↗

PubMed2006

Selected sleep disorders: restless legs syndrome and periodic limb movement disorder, sleep apnea syndrome, and narcolepsy.

Sleep disorders, including restless legs syndrome and periodic limb movement disorder, sleep apnea syndrome, and narcolepsy, are prevalent medical conditions, likely to be seen by practicing psychiatrists. Awareness of these conditions and their presentations, pathophysiology, and treatment allows psychiatrists to treat these conditions where appropriate, to minimize complications and health consequences associated with delayed diagnosis, and to reduce the burden of disease that these conditions may place on patients already experiencing primary psychiatric disorders.

Continuous Positive Airway Pressure↗

PubMed2004

[Diagnosis and therapy of restless legs syndrome in the doctor's office].

BACKGROUND: Restless legs syndrome (RLS) is a movement and sleep disorder with leg dysesthesias with a high prevalence (9-18% in Austria). AIM OF THE STUDY: Determination of frequency, diagnosis and therapy of RLS in general practitioner and specialist offices. METHODS: Telephone survey of a random sample of 120 general practitioners, 100 neurologists and 80 specialists in internal medicine. RESULTS: 69% of the whole sample of doctors reported seeing 1 to 10 RLS patients, but in proportion to the prevalence of these two conditions fewer cases of RLS than of Parkinson's disease are treated. In all three groups of doctors, 84% consider the 4 key symptoms (urge to move the legs accompanied or caused by dysesthesia; worsening of symptoms at rest or inactivity; relief by activity; worsening of symptoms in the evening/at night) the most important diagnostic criteria for RLS, followed by a complaint of disturbed sleep (75%), daytime tiredness (43%) and dopaminergic responsiveness in a therapeutic trial (29%). 83% of general practitioners and 86% of medical specialists refer their RLS patients to a neurologist, 19% to a polysomnographic examination. 75% of doctors decide for pharmacological treatment of RLS, 18% for psychotherapy, 15% for household remedies. 54% of all doctors (70% of the neurologists, 68% of the GPs, 48% of the medical specialists) prescribe dopamine agonists. L-Dopa is used by 49% (61% of the neurologists, 42% of the GPs, 44% of the medical specialists). 17% prescribe GABAergic drugs, 6% opiates. 51% would be highly interested in obtaining a drug specifically registered for the treatment of RLS. CONCLUSION: RLS is not as well known as Parkinson's disease. Thus providing doctors with relevant information and further education programs on this subject seems desirable. In Austrian doctors' offices the diagnosis of RLS is usually obtained clinically on the basis of the 4 key symptoms. Patients suffering from insomnia of multifactorial pathogenesis should be referred to an outpatient clinic for sleep disorders with an associated sleep laboratory. Especially neurologists and GPs consider dopamine agonists the treatment of first choice, closely followed by L-Dopa.

Adolescent↗

PubMed2004

The 14q restless legs syndrome locus in the French Canadian population.

A new restless legs syndrome locus on chromosome 14 recently has been reported in one family of Italian origin. Our study aimed to replicate this finding and determine the importance of this locus in the French Canadian population. Markers spanning the region were genotyped in 14 large families and linkage assessed using two-point and multipoint logarithm of odds scores. Possible linkage to this locus was found in one of our kindreds providing support for the existence of this locus and indicating that this locus may be responsible for a small fraction of French Canadian restless legs syndrome.

Canada↗

PubMed2007

Augmentation of restless legs syndrome with long-term tramadol treatment.

Restless legs syndrome (RLS) augmentation, defined as a kind of suppression of the circadian rhythm of the disease in which sensory and motor symptoms appear earlier during the day (and over previously unaffected body parts), with a progressive phase advance until, backwards, the symptoms may cover the entire day, has been described only after treatment with dopaminergic drugs. We report clinical and polysomnographic accounts of a patient developing RLS augmentation after long-term treatment with tramadol, an opioid agonist with selectivity for mu-receptor and added norepinephrine and serotonin reuptake inhibition properties. Polysomnographic measures showed an improvement of RLS and a disappearance of diurnal sensory and motor RLS symptoms after tramadol was stopped. Our case confirms a recent retrospective report of augmentation of RLS after treatment with tramadol, and begs the question whether augmentation is truly restricted to dopaminergic drugs.

Aged, 80 and over↗

PubMed2000

Clinical correlates of 6-hydroxydopamine injections into A11 dopaminergic neurons in rats: a possible model for restless legs syndrome.

Pursuant to the clinical suspicion that restless legs syndrome (RLS) may involve dopaminergic diencephalic spinal neurons (A11), we performed stereotaxic bilateral 6-hydroxydopamine (6-OHDA) lesions into the A11 nucleus to observe for any behavioral correlates similar to this clinical condition. Pathologic examination demonstrated a 54% reduction in A11 tyrosine hydroxylase staining cells in rats injected with 6-OHDA versus sham treatment. Multiple blindly rated 90-120-minute video epochs demonstrated an increased average number of standing episodes (14.4+/-11.7 versus 7.3+/-5.5 episodes/epoch) and increased total standing time (38.9+/-20.5 versus 25.3+/-12.2 minutes/epoch) but similar total sleep time in four lesioned rats when compared with two sham rats. Treatment of the lesioned rats with intramuscular pramipexole subsequently resulted in fewer standing episodes (4.4+/-3.3 versus 14.4+/-11.7 episodes/epoch) and less total standing time (20.9+/-12.3 versus 38.9+/-20.5 minutes/epoch) when compared with untreated lesioned rats. Despite a large number of observations, the small number of lesioned animals precluded formal statistical analysis. These behaviors are consistent, although not specific, with what would be expected in an animal model of RLS.

Adrenergic Agents↗

PubMed2006

Epidemiology of restless legs syndrome: the current status.

Epidemiological studies in restless legs syndrome (RLS) have often been limited by misdiagnosis and by the fact that affected individuals, even when their symptoms are severe, might not seek medical care. Some of these limitations have been overcome in the last years as population studies based on face to face interviews have been carried out with new standardized diagnostic criteria. According to these studies, and in contrast to earlier views, RLS has been shown to be a common disorder with prevalences ranging between 2.5 and 10% of the population. Although few studies performed outside Europe/North America have shown a low prevalence, a number of methodological issues have been raised that might question these results. Furthermore, once established, RLS usually follows a chronic course, and preliminary evidence shows that it might worsen over time in some patients. Endstage renal disease, increasing age, female gender, pregnancy, frequent blood donations, iron deficiency and neuropathy are considered to be risk factors for this disorder. The association to RLS is less definitely established for other conditions, such as PD or diabetes. In summary, epidemiological evidence suggests that RLS is a common neurological disorder-with high impact on many aspects of the life of those affected.

Adult↗