Controlled withdrawal of pramipexole after 6 months of open-label treatment in patients with restless legs syndrome.

Although dopamine agonists are becoming first-line therapy for restless legs syndrome (RLS), few reports describe treatment periods exceeding 12 weeks. Here, 150 RLS patients who had responded to pramipexole during a 6-month run-in period (mean dose, 0.50 mg) were randomly assigned to receive placebo or continue receiving pramipexole at an individually optimized dose of 0.125 to 0.75 mg/day for a further 3 months. Patients switched to placebo reached the primary endpoint (a predefined worsening on both the Clinical Global Impressions-Global Improvement scale and the International RLS Study Group Rating Scale) significantly more often than patients who continued to receive pramipexole (85.5% vs. 20.5%; P < 0.0001). They also reached the primary endpoint faster, in 5 versus 42 days to a Kaplan-Meier survival estimate of 0.85 and 7 versus > 84 days to an estimate of 0.5. Over the total 9 months, clinician and patient ratings of symptoms, sleep, and quality of life identified no decline in pramipexole's benefit or tolerability. The great majority of adverse events (AEs) were mild or moderate, and of expected types. Augmentation was considered an AE, but in this population of responders it did not occur.     

Long-term treatment with pramipexole in restless legs syndrome

The aim of the present study was to look at the long-term efficacy and side effects profiles of pramipexole in a large cohort of drug naïve patients with regard to dopaminergic medications. In all, 195 consecutive restless legs syndrome (RLS) patients who were prescribed pramipexole more than 1 year previously, agreed to undergo a telephone interview to assess both the efficacy and side effects of pramipexole. Forty-three patients had discontinued pramipexole: 20 because of side effects, six because of a lack of efficacy, six for both and 11 for other reasons. Patients who continued pramipexole for more than 1 year ( n  = 152) reported a mean decrease in RLS symptoms severity of 80.9% (SD = 19.6%). At the onset of treatment, the most common side effects were nausea (30%), tiredness (9%), dizziness (8%), headache (4%), insomnia (3%), dry mouth (2%), difficulty to concentrate (1.3%) and sleepiness (0.7%), At 30 months, most patients ( n  = 124/152; 81.6%) reported an absence of side effects of pramipexole. None of the adverse effects occurred in more than 5% of patients at follow-up. The present study confirms, in a large cohort of unselected patients, that pramipexole is effective and safe in the long-term treatment of RLS.     

Restless legs syndrome and polyneuropathy.

Restless legs syndrome (RLS), diagnosed according to the International RLS Study Group criteria, was investigated in 97 consecutive patients with polyneuropathy and found in 29 patients. RLS patients were more often women (22 of 29 vs. 33 of 68; P = 0.015), mainly with sensory neuropathy of small fiber type (15 of 29 vs. 16 of 68; P = 0.009). Changes of sensory action potentials were significantly less severe in RLS patients. In the RLS group, acquired neuropathies, and in particular dysimmune neuropathies, were significantly more frequent (27/29 vs. 46/68; P = 0.009). Thus, RLS is frequent in acquired polyneuropathy of sensory type and mild entity, mainly in women.     

Restless legs syndrome: an overview of the current understanding and management

Over the last few years, major progress in research has improved our understanding of the restless legs syndrome (RLS). Although frequently under-diagnosed, several epidemiological studies have estimated its prevalence in western countries at 4-10% of the general population. Its diagnosis is usually made on a clinical basis, according to the criteria established by the International RLS Study Group (Mov Disord 1995; 10:634). Furthermore, major advances have also been achieved regarding our understanding of the pathophysiology of the disorder. Thus, several brain imaging studies, as well as pharmacological challenges, suggest the presence of a dopaminergic dysfunction playing a major role in its causation. In addition, a strong association has been discovered between brain iron deficiency and RLS. Eventually, dopaminergic drugs have shown therapeutic efficacy in various large-scale therapeutic trials, and, today, dopaminergic agonists represent the first line of treatment. In conclusion, these and other recent findings shed light on our understanding and management of one of the most common movement disorders.     

Efficacy of pramipexole in restless legs syndrome: a six-week, multicenter, randomized, double-blind study (effect-RLS study).

We evaluated the efficacy of pramipexole versus placebo in restless legs syndrome (RLS) for 6 weeks. Overall, 345 patients were randomly assigned in a 1:2 ratio to receive either placebo (n = 115) or pramipexole (n = 230) with a starting dose of 0.125 mg/day. The dose was individually optimized according to the Patient Global Impression (PGI) assessment, up to a maximum of 0.75 mg/day. The primary endpoint consisted of two assessments: the change from baseline in the International RLS Study Group Rating Scale (IRLS) and the proportion of patients with Clinical Global Impressions-Improvement (CGI-I) assessments of "much/very much improved" (CGI-I responders) at week 6. Secondary endpoints included PGI and IRLS responder rates. Patient demographics and baseline characteristics were comparable between treatment groups. At baseline, mean IRLS scores were 24.9 (placebo) and 24.7 (pramipexole), representing severely affected patients. After 6 weeks, adjusted mean reductions (+/-SE) in IRLS score were 5.7 (+/-0.9) for placebo (median dose 0.47 mg/day) and 12.3 (+/-0.6) for pramipexole (median dose 0.35 mg/day; P < 0.0001). CGI-I responder rates were 32.5% (placebo) and 62.9% (pramipexole) (P < 0.0001). For all secondary endpoints, pramipexole showed superior results. Pramipexole was well tolerated throughout the study.     

Restless legs syndrome and paroxetine

Restless legs syndrome is a frequent dyssomnia with well-known clinical features but uncertain origin and treatment. This paper describes a case of restless legs syndrome worsened by paroxetine. A possible pathogenic hypothesis related to the attributed neurochemical properties of the drug is proposed.     

Restless legs syndrome and pregnancy: prevalence,possible pathophysiological mechanisms and treatment

Restless legs syndrome (RLS) is a common sleep disorder that may be associated with pregnancy. Studies have found that the prevalence of RLS among pregnant women ranged from 10 to 34%. Typically, there is complete remission of symptoms soon after parturition; however, in some patients, they may continue postpartum. RLS has been shown to be associated with a number of complications in pregnancy including preeclampsia and increased incidence of Cesarean sections. Although multiple hypotheses have been proposed to explain this association, each individual hypothesis cannot completely explain the whole pathogenesis. Present understanding suggests that a strong family history, low serum iron and ferritin level, and high estrogen level during pregnancy might play important roles. Vitamin D deficiency and calcium metabolism may also play a role. Medical treatment of RLS during pregnancy is difficult and challenging considering the risks to mother and fetus. However, in some cases, the disease may be severe enough to require treatment.     

Restless legs syndrome and Parkinson's disease in men

We examined whether men with restless legs syndrome (RLS) have a higher prevalence of Parkinson's disease (PD) among 23,119 US participants of the Health Professional Follow‐up Study who were free of diabetes and arthritis. RLS was assessed using a set of standardized questions recommended by the International RLS Study Group. PD cases were identified by self‐reported questionnaires and confirmed by review of medical records. Compared to men without RLS, multivariate‐adjusted odds ratios for PD were 1.1 (95% confidence interval: 0.4, 3.0) for men with RLS symptoms 5–14 times per month and 3.09 (95% confidence interval: 1.5, 6.2; P trend = 0.003) for those with symptoms 15 times or more per month, after adjusting for age, smoking, use of antidepressant, and other covariates. In conclusion, men with RLS are more likely to have concurrent PD. Prospective studies are warranted to clarify the temporal relationship between RLS and PD. © 2010 Movement Disorder Society     

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.     

Restless legs syndrome in Parkinson's disease

We aimed to investigate the prevalence of restless legs syndrome (RLS) according to essential diagnostic criteria, and to explore potential associations with clinical features, especially motor fluctuations, in a cohort of 113 patients with idiopathic Parkinson's disease (PD). Twenty‐eight (24%) fulfilled essential diagnostic criteria for RLS. They were younger (63.1 ± 8.6 vs. 68.8 ± 9.0 years; P = 0.004), had an earlier onset of PD (54.1 ± 9.5 vs. 59.2 ± 10.3 years; P = 0.018), and received lower levodopa equivalent doses (578.4 ± 382.2 vs. 779.1 ± 459.6 mg/day; P = 0.04) than patients with PD who scored negative for RLS. In 23 patients (82%), RLS symptom onset was after PD onset (mean interval, 4.5 ± 3.7 years). The majority (n = 17, 61%) who scored positive for RLS reported that the urge to move the legs and unpleasant sensations were associated with wearing off, raising the possibility of RLS mimics in fluctuating patients with PD. © 2009 Movement Disorder Society     

Actometry in measuring the symptom severity of restless legs syndrome.

In a previous, controlled study we demonstrated that the general lower limb activity measured by three-channel actometry is a promising objective measure of restless legs syndrome (RLS) severity. In the present study we have further evaluated the method in measuring RLS symptom severity in an open, single-day pramipexole intervention with 15 RLS patients. Both our standardized actometric parameters (nocturnal lower limb activity and controlled rest activity) decreased significantly during the intervention in parallel with the subjectively reported relief of RLS symptoms.     

Restless legs syndrome is a common feature of adult celiac disease

Restless legs syndrome (RLS) is a common neurological condition, frequently idiopathic, sometimes associated with specific disorders such as iron deficiency. We investigated RLS prevalence in celiac disease (CD), an autoimmune disease characterized by several features such as malabsorption‐related iron deficiency anemia and peripheral neuropathy. We screened a population of 100 adult CD patients for CD features, iron metabolism, clinical and neurological conditions, and enrolled 100 age‐ and sex‐matched controls in the general population. RLS was ascertained in CD patients and controls by both the presence of the four essential International RLS Study Group diagnostic criteria and neurological examination. The International RLS Study Group rating scale was used to measure RLS severity. We found a 31% prevalence of RLS in the CD population that was significantly higher than the prevalence in the control population (4%; P < 0.001). The average severity of RLS in CD population was moderate (17 ± 6.5). In the CD population, no significant correlation was found between RLS and either gluten‐free diet or iron metabolism, despite hemoglobin levels were significantly lower in CD patients with RLS than without RLS (P = 0.003). We found no correlation between RLS and other possible causes of secondary RLS, including signs of peripheral neuropathy, pregnancy, end‐stage renal disease, and pharmacological treatments.Our study broadens the spectrum of neurological disorders associated with CD and indicates that RLS should be sought for in all patients with CD. © 2010 Movement Disorder Society     

Restless legs syndrome is frequently overlooked in patients being evaluated for polyneuropathies

Restless legs syndrome (RLS) often presents with paresthesias and dysesthesisas. We have investigated the prevalence and clinical features of RLS in a cohort of patients referred for clinical suspicion of peripheral neuropathy (PN). Sixty-four patients with sensory symptoms, and 101 age-matched controls were prospectively evaluated for RLS, PN and causes of both conditions. In the 64 patients (60 ± 14 years), none were referred with a suspicion of RLS. Forty-one had a sensori-motor PN of which 22 had a definite RLS (54%). When excluding other causes of RLS, 8 of 41 patients had a RLS associated with a neuropathy (20%). The proportion of RLS in the healthy controls was 10%, lower than in the cohort of patients. In patients without PN, 57% had a RLS, and 55% in the whole cohort, a higher proportion than in the healthy controls ( P  < 0.0001). Patients with PN and RLS had more sleep disorders ( P  < 0.04), and legs and calves symptoms ( P  = 0.09) than patients with PN without RLS. Toes symptoms were more frequently observed in patients with PN but without RLS ( P  < 0.02). We conclude that RLS frequently presents with symptoms suggestive of peripheral neuropathy, and therefore, is often overlooked.