Apomorphine in idiopathic restless legs syndrome: an exploratory study

BACKGROUND: Dopaminergic and opioidergic drugs have been found to be effective in patients with restless legs syndrome (RLS). OBJECTIVES: To test the effect of apomorphine--a combined opioidergic and dopaminergic agonist--and subsequent selective antagonism by naloxone and metoclopramide on subjective and objective symptoms in patients with idiopathic RLS. METHODS: Nine patients with RLS were pretreated with oral domperidone for three days. A modified suggested immobilisation test (SIT) was carried out between 8 pm and 1 am under the following conditions of intravenous drug administration: baseline-apomorphine-apomorphine plus naloxone-apomorphine plus metoclopramide. Outcome variables were a visual analogue scale (VAS) of subjective RLS symptoms and EMG documented periodic leg movements while awake (PLMW). RESULTS: Compared with baseline, apomorphine resulted in a rapid and significant improvement in subjective RLS symptoms as measured by VAS (54.5% improvement; p = 0.011), and an almost immediate cessation of PLMW, measured by PLMW index (98.0% improvement; p = 0.012). Neither additional naloxone nor metoclopramide blocked this effect significantly. While given apomorphine with metoclopramide, there was a trend to reappearance of PLMW. CONCLUSIONS: Apomorphine may be an effective treatment for idiopathic RLS. Its effectiveness may reflect both to its dopaminergic and its opioidergic activity, and is not diminished significantly by blocking only one of these pathways. The trend to a worsening of the PLMW index with metoclopramide hints at a primarily dopaminergic effect of apomorphine in idiopathic RLS.     

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.     

Gabapentin versus ropinirole in the treatment of idiopathic restless legs syndrome

Dopaminergic agents such as ropinirole are the drugs of first choice in treating restless legs syndrome (RLS). Recently, gabapentin, a structural analogue of gamma-aminobutyric acid, has also been shown to improve sensorimotor symptoms in RLS. Therefore, the tolerability and efficacy of randomized treatment with either gabapentin or ropinirole in patients with idiopathic RLS was evaluated in this 4-week open clinical trial. Patients with idiopathic RLS were treated with either 300 mg of gabapentin (n = 8) or 0.5 mg of ropinirole (n = 8) as the initial dose, and the dose was up-titrated until relief of symptoms was achieved (gabapentin mean dosage 800 +/- 397 mg, range 300-1,200 mg; ropinirole mean dosage 0.78 +/- 0.47 mg, range 0.25-1.50 mg). In both groups, International Restless Legs Syndrome Study Group questionnaire scores improved significantly (p < or = 0.018), whereas the scores of the Epworth sleepiness scale remained unchanged within normal limits. Polysomnographic data showed a reduction of periodic leg movements during sleep (PLMS; p < 0.03) and PLMS index (p < 0.02) in both groups. Side effects were only mild and mostly transient. After 6-10 months of follow-up, in most patients, RLS symptoms were still improved. We conclude that gabapentin and ropinirole provide a similarly well-tolerated and effective treatment of PLMS and sensorimotor symptoms in patients with idiopathic RLS.     

Levodopa for idiopathic restless legs syndrome: evidence-based review.

Restless legs syndrome (RLS) is a sensory motor disorder characterized by a distressing urge to move the legs and sometimes also other parts of the body usually accompanied by a marked sense of discomfort or pain in the leg or other affected body part. The prevalence of RLS is estimated at 2.7 to 5% of adults and it is more common in women. The treatment of RLS with levodopa has been reported thus a systematic synthesis of evidence is necessary to evaluate the effectiveness and safety of levodopa for RLS. Systematic review of randomized or quasi-randomized, double blind trials on levodopa. Relief of restless legs symptoms marked on a validated scale, subjective sleep quality, sleep quality measured by night polysomnography and actigraphy, quality of life measured by subjective measures, adverse events associated with the treatments. Nine eligible clinical trials were included. The subjective analyses of these studies showed contradictory results, although the objective analyses showed that treatment group had a statistically significant improvement of periodic leg movement (PLM) index, favoring the treatment group. The most commonly adverse event seen was gastrointestinal symptoms. The short-term treatment with levodopa was demonstrated effective and safety for PLM, but there was only few trials assessing long-term treatment and the augmentation phenomenon in RLS. Further long-term randomized controlled trials using standard follow-up measurements as the International RLS Study Group Rating Scale are necessary.     

Prevalence and clinical profile of restless legs syndrome in Parkinson's disease

Parkinson's disease (PD) and restless legs syndrome (RLS) have a dopaminergic link. More insight in the clinical profile of RLS in patients with PD may benefit our understanding of this link. The aims of this study were to evaluate the frequency and clinical profile of RLS in a large cohort of PD patients. In 269 nondemented Caucasian PD patients, the four diagnostic criteria for RLS were administered by a RLS trained researcher. In patients with definite RLS, the severity of these symptoms was assessed. Furthermore, in all patients, relevant motor and nonmotor symptoms in PD were evaluated. Definite RLS was present in 11% of the patients. RLS patients were more often female (69% vs. 32%, P < 0.001), but no other significant differences existed between PD patients with and without RLS. Within the PD patients with RLS, severity of RLS correlated positively with PD severity, motor fluctuations, depressive symptoms, daytime sleepiness, cognitive problems, autonomic symptoms, and psychotic symptoms. This study in a large PD cohort shows that prevalence of RLS is similar to that in the general population, which might be caused by underestimation of RLS due to dopaminergic treatment. No relations were found between the presence of RLS and PD symptoms, but the severity of RLS was related to the severity of PD‐related, mainly nondopaminergic, symptoms. It is hypothesized that, nondopaminergic systems, such as the noradrenergic system may play a role in the possible link between PD and RLS. © 2010 Movement Disorder Society     

继发性不宁腿综合征

本文回顾继发性不宁腿综合征的相关研究结果,介绍其常见病因。经研究显示,有多种因素可能与继发性不宁腿综合征的发生发展和严重程度相关,如肾衰竭、脊髓和周围神经病变、妊娠所致铁和叶酸缺乏及相应性激素变化;帕金森病多巴胺能系统功能紊乱;某些药物（抗抑郁药、抗精神病药、组胺受体阻断药）;吸烟、饮酒;咖啡因;偏头痛等。临床应详细询问病史,去除病因,提高患者生活质量。     

Olanzapine-induced restless legs syndrome

Only nine patients with olanzapine-induced restless legs syndrome (RLS) have been reported in the literature to our knowledge. We describe two patients with olanzapine-induced RLS treated at our hospital and review the nine reported patients. There were five women and six men aged between 28 and 62 years in the overall group. RLS symptoms emerged at olanzapine doses between 2.5 and 20 mg. The symptoms improved in all patients when the dose was reduced and immediately disappeared when the medication was stopped. International Restless Legs Scale (IRLS) scores ranged from 10 to 35. Three patients had a family history of idiopathic RLS. Supplemental drugs were administered to control RLS symptoms in five patients. Ropinirole was effective in one patient, while two patients did not respond to the drug. Propoxyphene effectively relieved symptoms in one patient who did not respond to ropinirole or clonazepam. RLS symptoms did not recur following substitution of other antipsychotic drugs for olanzapine. In conclusion, olanzapine can induce RLS, particularly in patients with a family history of idiopathic RLS. More than half of the patients experienced severe to very severe symptoms. A dose-dependent relationship was observed between olanzapine and RLS symptoms. A gradual increase in dose may prevent olanzapine-induced RLS. The optimal treatment for olanzapine-induced RLS is discontinuation of olanzapine.     

Iron deficiency with normal ferritin levels in restless legs syndrome

This report describes a patient with iron deficiency in bone marrow examination and iron-responsive restless legs syndrome (RLS), in whom serum ferritin levels were well above the conventional cutoff for considering iron deficiency. The predictive value of serum ferritin for iron deficiency in RLS depends on the cutoff employed, on the pre-test likelihood of iron deficiency and on coexisting inflammatory conditions. Bone marrow examination is helpful when ferritin levels are equivocal.     

Childhood-onset restless legs syndrome

The clinical characteristics of childhood-onset restless legs syndrome are described. Thirty-two of 538 subjects (5.9%) examined in our sleep disorders center received diagnoses of restless legs syndrome. They were classified based on published criteria into probable (n = 9/32 or 28%) and definite (n = 23/32 or 78%) categories. Apart from an earlier age of diagnosis of the probable group, no differences were found between the two categories. Sleep onset or sleep maintenance insomnia was the most common symptoms, being present in 28 of 32 subjects (87.5%). Inattentiveness was seen in 8 of 32 subjects (25%). Serum ferritin levels were measured in 24 of 32 subjects and were below 50 microg/L in 20 of 24 subjects (83%). A family history of restless legs syndrome was present in 23 of 32 (72%) subjects, with mothers almost three times more likely to be affected than fathers (p = 0.02). We conclude that iron deficiency and a strong family history are characteristic of childhood-onset restless legs syndrome.     

Homocysteine in restless legs syndrome

BACKGROUND AND PURPOSE: Total plasma homocysteine (tHcy) may be a risk factor for vascular diseases and is associated with renal failure or deficiency of vitamin B12 or folate. Recently, elevated tHcy concentrations were observed in patients with Parkinson's disease (PD), particularly those under levodopa treatment. Our objective was to determine whether changes in tHcy are also found in patients with restless legs syndrome (RLS) in relation to levodopa treatment and whether folate and vitamins B6 and B12 play a role in RLS. METHODS: In a total of 228 subjects, tHcy and B vitamin status (vitamins B6 and B12, folate) were studied: 97 patients with idiopathic RLS (40 under levodopa therapy), 39 with PD (25 under levodopa therapy), and 92 healthy controls adjusted for age and gender. RESULTS: No significant differences were observed in tHcy levels between RLS patients and controls or between the RLS groups without treatment or with levodopa or dopamine agonist treatment. Mean tHcy was significantly higher in PD patients (13.8 micromol/l) than in either RLS patients (11.7 micromol/l) or controls (11.0 micromol/l; p<0.001). There was an inverse association between tHcy and vitamin B12 in each group. CONCLUSIONS: RLS and, in particular, levodopa treatment in RLS are not associated with hyperhomocysteinemia. Elevated tHcy could, however, be confirmed in PD patients.