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.     

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。     

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.     

The restless legs syndrome

The restless legs syndrome is a common disorder that encompasses an idiopathic form of genetic or unknown origin and symptomatic forms associated with many causes. Symptomatic forms occur during pregnancy and are coincident with uraemia, iron depletion, polyneuropathy, spinal disorders, and rheumatoid arthritis. For the hereditary forms, at least three gene loci, located on chromosomes 12, 14, and 9, have been traced so far. Prevalence in the general population is between 3% and 9%, increases with age, and is higher in women than in men. Treatment is needed only in the moderate to severe forms of the disorder and mostly in elderly people. Pathophysiology and treatment may be closely linked to the dopaminergic system and iron metabolism. Dopaminergic treatment with levodopa and dopamine agonists is the first choice in idiopathic restless legs syndrome, but augmentation and rebound should be monitored in long-term treatment. Various other drugs, such as opioids, gabapentin, and benzodiazepines, provide alternative treatment possibilities.     

Genetics of restless legs syndrome

Restless legs syndrome (RLS) is a highly familial trait with heritability estimates of about 50%. It is a polygenetic disorder in which a number of variants contribute to the phenotype. Linkage studies in families with RLS revealed several loci but have not yet led to the identification of disease-causing sequence variants. Phenocopies, nonpenetrance, and possible intrafamilial heterogeneity make it difficult to define the exact candidate region. Genome-wide association studies identified variants within intronic or intergenic regions of MEIS1, BTBD9, and MAP2K5/LBOXCOR1. Carriers of one risk allele had a 50% increased risk of developing RLS. MEIS1 and LBXCOR1 are developmental factors and raise new pathophysiologic questions for RLS. These variants have weak and moderate effects and increase the risk of developing RLS. It is still possible that strong effects explain the occurrence of RLS in families. Therefore, linkage and association studies should be used congruently to dissect the complete genetic architecture of RLS.     

Genetics of restless legs syndrome

Several studies on restless legs syndrome (RLS) have suggested a substantial genetic contribution in the etiology of this sleep disorder. Clinical surveys of idiopathic RLS patients have shown that 40-90% report a positive family history. The clinical features have been compared between familial and sporadic cases and the only difference found was a younger age-at-onset in familial RLS. Despite several reports suggesting a genetic contribution to the etiology of idiopathic RLS, few molecular genetic studies have been carried out attempting to identify genes that can predispose to this disorder. In particular, genes encoding for the GABA A receptor subunits, the gene for the alpha1 subunit of the glycine receptor, and genes involved in dopaminergic transmission and metabolism have been analyzed, however no significant findings have been reported. Genomewide linkage analysis studies using microsatellite markers have identified three loci for RLS: on chromosome 12q, on chromosome 14q and on chromosome 9p. It is important to investigate whether further RLS families show linkage to one of these loci to discuss the contribution of these loci and to provide a prerequisite of a mutational screening and identification of the RLS genes.     

Aetiopathogenesis of restless legs syndrome

Neurological Sciences - The pathogenesis of restless legs syndrome (RLS) is not yet completely understood. However, recent research addressed the hypothesis that dopaminergic pathways are involved...     

Idiopathic restless legs syndrome:

Abstract. Objectives Neurophysiological studies have shown an impairment of temperature perception in secondary and idiopathic restless legs syndrome (RLS). It is unclear whether these deficits are caused by peripheral nerve fibre damage or by central impairment of somatosensory processing. The aim of the present study was (1) to determine the frequency of thermal hypaesthesia in a large population of secondary and idiopathic RLS patients; (2) to differentiate between a peripheral and central disturbance of somatosensory processing and (3) to correlate these findings with the clinical manifestation of the disease. Methods From the results of clinical examination, nerve conduction studies and blood samples the patients were divided into secondary and idiopathic RLS groups. The severity of RLS symptoms was assessed by standardized questionnaires. Quantitative sensory testing (QST) assessing temperature perception was performed in all patients. The peripheral function of small nerve fibres was evaluated by the quantitative nociceptor axon reflex test (QNART). Results 22 secondary and 20 idiopathic RLS patients participated in the study. Impairment of temperature perception (QST) was found in 72% of the secondary RLS patients and in 55% of idiopathic RLS patients. The peripheral C–fibre function (QNART) was normal in idiopathic RLS patients. In contrast it was significantly impaired in secondary RLS patients compared with idiopathic RLS patients and age matched controls. There was no correlation between the results obtained in QST and clinical scores. Conclusion Impairment of temperature perception is present in a high percentage of RLS patients. In secondary RLS the sensory deficits are at least in part caused by small fibre neuropathy. In idiopathic RLS a functional impairment of central somatosensory processing is present.     

帕金森病与不宁腿综合征

帕金森病为慢性进行性神经系统变性疾病，典型临床症状包括运动迟缓、静止性震颤、强直以及姿势平衡障碍。不宁腿综合征（restless legs syndrome，RLS）系指出现在腿部的不适感导致难以控制的移动下肢的冲动，多发生在夜间并由此而产生睡眠障碍。早在19世纪，《震颤麻痹》一书中就已首次提出帕金森病患在夜间会出现频繁的肢体运动。近年来不断有研究报道，帕金森病患不宁腿综合征的发病率高于普通人群，提示二之间可能存在某种联系。[第一段]     

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.