Cause Of Restless Legs Syndrome Research Articles

Anaesthesia and restless legs syndrome

Editor, A 67-year-old woman presented for left breast needle localized excision biopsy. Her hypertension was controlled by diltiazem, bendrofluazide, and irbesartan. She had had restless legs syndrome (RLS) since the age of 13 and took pramipexole (a dopamine agonist) 125 μg once daily for this, usually in the late afternoon, when her symptoms were worst. She was not aware of any anaesthetic problems previously. Preoperatively, she had self-administered her antihypertensive medication, but not her pramipexole because she was symptom free. After placement of standard monitoring equipment, a 20G cannula was inserted into the dorsum of her right hand. Immediately after preinduction, her blood pressure (BP) was 160/90 mmHg. After preoxygenation, anaesthesia was induced with 75 μg fentanyl and 240 mg propofol. A size-4 disposable laryngeal mask airway was inserted, and spontaneous respiration continued throughout the anaesthetic, which was maintained using sevoflurane in an air/oxygen mixture (FiO2 0.6). One litre of Hartmann's solution and 50 mg cyclizine was administered intravenously. Five minutes after skin incision, her BP increased to 180/100 mmHg. She received a further 25 μg fentanyl, 1 g of paracetamol and 75 mg diclofenac sodium intravenously, and the monitored minimum alveolar concentration of sevoflurane was increased from 1.1 to 1.3. Her BP remained between 160/90 and 190/100 mmHg for the duration of the half-hour procedure. Her heart rate was 75–85 beats min−1 and her respiratory rate was 19–24 beats min−1. The wound was infiltrated with 20 ml of 0.5% bupivacaine after skin closure. On rapid emergence from anaesthesia, she was very agitated, complaining of pain in her legs relieved slightly by vigorous movement. She was administered 30 mg dihydrocodeine orally and 125 μg of oral pramipexole. Thirty minutes later, she reported good relief from her leg pains and her BP gradually settled to 120/60 mmHg. RLS affects 7–10% of adults (0.5–1% children) of mainly European origin, with increased prevalence among women and patients aged 60–70 years. The condition is under-recognized in the surgical population. Aetiologically, genetic and environmental factors are implicated: familial inheritance is seen, but a specific gene has not been found and specific causation remains uncertain [1]. RLS may be a primary condition, or be secondary to iron deficiency, renal failure, pregnancy, or the use of certain medications (dopamine antagonists, neuroleptics, selective serotonin reuptake inhibitor and tricyclic antidepressants, antihistamines, caffeine, alcohol, nicotine) [2]. The diagnosis is clinical, requiring an urge to move the legs (and less commonly other parts of the body) usually accompanied by an uncomfortable sensation, occurrence at rest, improvement with activity, and worsening of symptoms in the evening or at night. RLS has disruptive effects on sleep quality and daily life. Treatment of secondary causes of RLS may result in improvement or resolution of symptoms. Approximately one-third of patients require medication for symptomatic relief. Dopamine agonists (pramipexole, ropinirole, rotigotine), anticonvulsants (gabapentin), benzodiazepines (clonazepam, temazepam), and opioids (codeine, tramadol) may be beneficial. Patients with RLS should be scheduled for morning operating lists. Preoperatively, they should be encouraged to take their usual RLS medication. Premedication with benzodiazepines and opioids should be considered. Certain drugs can exacerbate the condition and should be avoided perioperatively, including butyrophenones (haloperidol, droperidol), sedative anihistamines (cyclizine – the likely cause of exacerbation in out patient), dopamine antagonist antiemetics (metoclopramide, prochlorperazine), and opioid antagonists (naloxone). 5-HT3 receptor antagonists should be used for antiemesis. Ketamine may be preferred for the induction of anaesthesia [3]. Involuntary leg movements may persist after the administration of spinal or epidural anaesthesia, but may be minimized by the addition of opioids to intrathecal or (continuous) epidural local anaesthesia. Anecdotally, intravenous magnesium [4] and physostigmine [5] have provided symptomatic control. The use of graduated compression stockings and calf compressors may also be beneficial [6]. Postoperatively, patients should be encouraged and assisted to mobilize early, and adequate (opioid) analgesia should be given, as immobility and pain can exacerbate symptoms [7]. Iron supplementation should be considered perioperatively, particularly when operative blood loss is likely to be significant.

Association between Antipsychotics-Induced Restless Legs Syndrome and Tyrosine Hydroxylase Gene Polymorphism

ObjectiveRestless legs syndrome (RLS) has been reported to be more prevalent in schizophrenic patients who take antipsychotics. The cause of RLS is unknown but associated with dopaminergic deficiency. Tyrosine hydroxylase (TH) is the enzyme responsible for catalyzing the conversion of L-tyrosine to DOPA. The purpose of this study is to determine whether the TH gene Val81Met polymorphism is associated with antipsychotic-induced RLS.MethodsOne hundred ninety Korean schizophrenic patients were evaluated by the diagnostic criteria of the International RLS Study Group (IRLSSG). The genotyping was performed by PCR-based methods.ResultsOf the one hundred ninety schizophrenic patients, 44 (23.2%) were found to have RLS. Although there were no significant associations between TH genotypes or allele frequencies and RLS, when separate analyses were performed by sex (male or female), we detected significant differences in the frequencies of the genotype (χ2=6.15, p=0.046) and allele (χ2=4.67, p=0.031) of the TH gene Val81Met polymorphism between those with and without RLS in the female patients.ConclusionThese findings suggest that the TH gene Val81Met SNP might be associated with antipsychotic-induced RLS in female schizophrenic patients.

Restless legs syndrome: an early manifestation of Huntington’s disease?

Far from being uniform, Huntington's disease (HD)'s phenotype encompasses a large variety of motor and non-motor symptoms which occur in various combinations in individual patients. To describe an unusual association between restless legs syndrome (RLS) and HD. We report a patient with an atypical presentation of genetically demonstrated HD, who developed typical RLS a few years prior to and during the course of HD. Common causes of RLS were excluded and the polysomnography confirmed frequent and severe periodic limb movements during sleep and while awake. We propose RLS as an uncommon but early feature of HD in some patients, and suggest adding HD to the already long list of RLS secondary to neurodegenerative conditions.

Restless Legs Syndrome in Patients with Chronic Obstructive Pulmonary Disease

To evaluate the prevalence of restless legs syndrome (RLS) in patients with chronic obstructive pulmonary disease (COPD) and the relationship between RLS and clinical/laboratory findings of COPD. One hundred and thirty-four COPD patients without secondary causes of RLS were included. Thirty-nine (29.1%) patients were diagnosed with RLS and classified as Group 1. The control group consisted of 65 age-matched COPD patients without RLS. Group 1 was divided into subgroups according to the Johns Hopkins Severity (JHS) scale. Patients with a score of 0, 1, or 2 were classified as JHS 0-2 and those with a score of 3 as JHS 3. Group 1 and the control group and subgroups were compared for clinical and laboratory characteristics. We found that the duration of COPD was longer and that airway obstruction, hypercapnia, and hypoxia were more evident in patients with RLS than those without. Similar differences were also detected between JHS subgroups 3 (more severe) and 0-2. Polyneuropathy frequency was significantly higher in Group 1 compared to controls. However, Group 1 subgroups showed a similar frequency of polyneuropathy. In a multivariate analysis, hypercapnia made a significant independent contribution to both JHS 0-2 and JHS 3 patients when RLS severity was set as the dependent variable. Polyneuropathy and the duration of COPD were significant independent variables for patients in the JHS 3 subgroup. Polyneuropathy was the strongest predictor for the JHS 3 patients. We conclude that RLS is frequent in COPD, particularly in patients with severe hypoxemia/hypercapnia and in late stages of the disease.

The effect of endovenous laser ablation on restless legs syndrome

Venous disease was proposed as a cause of restless legs syndrome (RLS) by Dr Karl A Ekbom in 1944, but has since remained largely unexplored. This study examines the effect of endovenous laser ablation (ELA) in patients with concurrent RLS and duplex-proven superficial venous insufficiency (SVI). Thirty-five patients with moderate to very severe RLS (as defined by the 2003 National Institute of Health (NIH) RLS criteria) and duplex-proven SVI completed an international RLS rating scale questionnaire (IRLS) and underwent standard duplex examination to objectively measure the baseline severity of their conditions. They were separated into non-operative and operative cohorts. The operative cohort underwent ELA of refluxing superficial axial veins using the CoolTouch CTEV 1320 nm laser and ultrasound-guided sclerotherapy of the associated varicose veins with foamed sodium tetradecyl sulphate (STS). All patients then completed a follow-up IRLS questionnaire. Baseline and follow-up IRLS scores were compared. Operative correction of the SVI decreased the mean IRLS score by 21.4 points from 26.9 to 5.5, corresponding to an average of 80% improvement in symptoms. A total of 89% of patients enjoyed a decrease in their score of > or =15 points. Fifty-three percent of patients had a follow-up score of < or =5, indicating their symptoms had been largely alleviated and 31% had a follow-up score of zero, indicating a complete relief of RLS symptoms. ELA of refluxing axial veins with the CTEV 1320 nm laser and foamed STS sclerotherapy of associated varicosities alleviates RLS symptoms in patients with SVI and moderate to very severe RLS. SVI should be ruled-out in all patients with RLS before initiation or continuation of drug therapy.

Association Study between Antipsychotics- Induced Restless Legs Syndrome and Polymorphisms of Dopamine D1, D2, D3, and D4 Receptor Genes in Schizophrenia

Objective: The cause of restless legs syndrome (RLS) is not yet clear, but more promising theories involve dopaminergic deficiency and genetic causes. This study investigated whether single-nucleotide polymorphisms in the genes of dopamine receptors DRD1, DRD2, DRD3 and DRD4 are associated with antipsychotics-induced RLS in schizophrenia. Methods: We evaluated 190 Korean schizophrenic patients using the diagnostic criteria of the International Restless Legs Syndrome Study Group and its rating scale for RLS. Genotyping was performed for the DRD1 gene –48A/G, DRD2 gene TaqI A, DRD3 gene Ser9Gly and DRD4 gene –521C/T single-nucleotide polymorphisms. The method of multifactor dimensionality reduction was used to analyze gene-gene interactions. Results: We classified the schizophrenic patients into 96 with and 94 without RLS symptoms. The genotype frequencies of all polymorphisms investigated did not differ significantly between these 2 groups. MDR analysis did not show a significant effect of the 4 dopamine receptor gene variants on susceptibility to antipsychotic-induced RLS symptoms (p > 0.05). Conclusions: These genetics data suggest that the analyzed polymorphisms of the dopamine genes may not be associated with RLS symptoms in schizophrenia. Confirming the results reported here requires a larger-scale study involving patients taking specific antipsychotics.

Restless Legs Syndrome Induced by Escitalopram: Case Report and Review of the Literature

Restless legs syndrome (RLS) is a sensorimotor disorder characterized by distressing sensations deep inside the limbs, typically occurring at bedtime or rest. These paresthesias involve an irresistible urge to move the limb, which provides temporary relief but at the expense of sleep and quality of life. The pathophysiology of RLS has been related to dopaminergic pathway dysfunction, thereby aligning it closely with depression from both pathophysiologic and treatment perspectives. Certain antidepressant drugs, including the selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs), may induce or exacerbate RLS. We describe the case of a 34-year-old woman with no history of RLS who came to the emergency department with acute decompensated heart failure. After 7 days of hospitalization, she was waitlisted to receive a heart transplant. Her mood became depressed, and she requested a psychiatric consultation; escitalopram 10 mg at bedtime was started. Within 2 days of starting therapy, she developed very severe (determined by a score based on an RLS symptom rating scale) RLS symptoms, warranting the discontinuation of escitalopram. Within 2 days of stopping therapy, her RLS symptoms improved considerably (rated as mild). One week later, the patient was rechallenged with a lower dose of escitalopram, and her very severe RLS symptoms reappeared. Within 2 days of stopping escitalopram, her RLS symptoms again improved, with complete resolution 1 week later. Using the Naranjo adverse drug reaction probability scale, which assesses the probability of a drug causing an adverse event, the patient's score was 9, indicating a definite adverse drug reaction. Although published case reports have linked fluoxetine, sertraline, citalopram, paroxetine, and mirtazapine to RLS, this is the first report, to our knowledge, of escitalopram as a cause of RLS. Based on this case and additional data published with other SSRIs and SNRIs, we believe that escitalopram should be added to the list of agents that can induce RLS.

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.

Characteristics and clinical correlates of restless legs syndrome in schizophrenia

Objective The cause of restless legs syndrome (RLS) has not yet been ascertained, but one of the most promising theories involves dopaminergic deficiency. In accordance with this theory, we assumed that the prevalence of RLS would be higher among schizophrenics treated with antipsychotics than in the normal population. The purpose of this study was to establish the prevalence, characteristics, and clinical correlates of RLS in schizophrenic patients undergoing treatment with antipsychotics. Methods A total of 182 hospitalized schizophrenic patients and 108 age- and sex-matched normal controls were enrolled. The presence of RLS and its severity were assessed using the International Restless Legs Syndrome Study Group (IRLSSG) diagnostic criteria and the IRLSSG rating scale, respectively. The Athens Insomnia Scale (AIS), Brief Psychiatric Rating Scale (BPRS), and Barnes Akathisia Rating Scale (BARS) were used to evaluate insomnia, global psychiatric symptoms, and akathisia, respectively, in schizophrenic patients. Results Of the 182 schizophrenic patients, 39 (21.4%) were found to have RLS and 87 (47.8%) met at least one of the RLS diagnostic criteria. The prevalence of RLS was significantly higher in the schizophrenia group than in the control group ( p = 0.009), as were the RLS scores ( p < 0.001). The BPRS ( p = 0.001) and the AIS ( p < 0.001) scores were higher in the RLS group than in the group with no RLS symptoms. Conclusion We conclude that it is important to consider the diagnosis of RLS when schizophrenic patients complain of insomnia, and that RLS symptoms could be associated with more severe psychiatric symptoms and insomnia.

The role of iron in restless legs syndrome

The impressive relief from restless legs syndrome (RLS) symptoms provided by levodopa treatment indicates RLS is caused by a dopaminergic abnormality. But similar and more lasting relief also occurs for iron treatment in some patients. Thus there are two major putative causes for RLS: CNS dopaminergic abnormality and CNS iron insufficiency. This article presents the data documenting that both peripheral and CNS iron insufficiency occur with RLS symptoms. Brain iron insufficiency is supported by independently replicated cerebrospinal fluid and brain imaging studies for patients without iron deficiency (ID) anemia. Autopsy studies and intravenous iron treatment further link brain iron insufficiency to RLS. The brain iron insufficiency in patients with RLS is now well established. In this article the data are reviewed that support the following postulates combining dopaminergic and iron causes of RLS: (1) All conditions that compromise iron availability will increase the risk of RLS leading to a higher than expected prevalence of RLS in these conditions. (2) Some patients with RLS have marginal CNS iron status that can become insufficient when deprived of normal access to adequate peripheral iron or may be insufficient even with normal access to adequate peripheral iron. (3) The change or reduced CNS iron status produces RLS symptoms largely through its effects on the dopaminergic system and the corollary to 3. (4) Dopaminergic system abnormalities producing RLS symptoms will be included in those produced by brain ID. Study of the iron model of RLS offers hope for developing new treatment approaches and perhaps methods to prevent or cure the disorder.

Considering the causes of RLS

The pathophysiology of restless legs syndrome (RLS) is complex and remains to be fully elucidated. The condition is predominantly a disorder of the central rather than the peripheral, nervous system, and dopaminergic dysfunction in subcortical systems appears to play a central role. Conditions associated with secondary RLS, such as pregnancy or end-stage renal disease, are characterized by iron deficiency, which suggests that disturbed iron homeostasis may also play a role in the development of the condition. Although most patients with RLS have normal serum ferritin levels, concentrations of ferritin and transferrin in the cerebrospinal fluid are reduced, suggesting iron deficiency within the central nervous system. Although iron is necessary for the activity of tyrosine hydroxylase, the rate-limiting step in dopamine synthesis, it is unclear whether this relationship plays a role in the aetiology of RLS. There also appears to be a genetic component, particularly when the condition develops before the age of 45 years. Candidate genetic loci have been located on chromosomes 9p, 12q and 14q, but the genes involved have yet to be identified. How these three identified aetiological factors, namely dopaminergic dysfunction, impaired iron homeostasis and genetic disposition, are inter-related in the genesis of RLS remains unclear.

Considering the causes of RLS

The pathophysiology of restless legs syndrome (RLS) is complex and remains to be fully elucidated. The condition is predominantly a disorder of the central rather than the peripheral, nervous system, and dopaminergic dysfunction in subcortical systems appears to play a central role. Conditions associated with secondary RLS, such as pregnancy or end‐stage renal disease, are characterized by iron deficiency, which suggests that disturbed iron homeostasis may also play a role in the development of the condition. Although most patients with RLS have normal serum ferritin levels, concentrations of ferritin and transferrin in the cerebrospinal fluid are reduced, suggesting iron deficiency within the central nervous system. Although iron is necessary for the activity of tyrosine hydroxylase, the rate‐limiting step in dopamine synthesis, it is unclear whether this relationship plays a role in the aetiology of RLS. There also appears to be a genetic component, particularly when the condition develops before the age of 45 years. Candidate genetic loci have been located on chromosomes 9p, 12q and 14q, but the genes involved have yet to be identified. How these three identified aetiological factors, namely dopaminergic dysfunction, impaired iron homeostasis and genetic disposition, are inter‐related in the genesis of RLS remains unclear.

Restless legs syndrome: Epidemiological and clinicogenetic study in a South Tyrolean population isolate

Genetic contributions to restless legs syndrome (RLS) have been consistently recognized from population and family studies. To determine the clinical and genetic features of RLS in a population isolate and explore linkage to three previously described susceptibility loci on chromosomes 12q, 14q, and 9p, respectively, an isolated population in the South Tyrolean Alps was identified and 530 adults participated in the study. Using a two-step strategy, 47 patients with idiopathic RLS were ascertained. The prevalence in the population was 8.9%. Twenty-eight patients (59.6%) had at least one affected first-degree relative and were classified as hereditary cases. In a single extended pedigree, linkage to known RLS loci was investigated specifying autosomal dominant and recessive models; parametric and nonparametric multipoint linkage scores were computed. None of the calculated linkage scores was suggestive of linkage between RLS and any of the three investigated loci. This study was conducted in a population isolate providing for a homogeneous genetic and environmental background. The absence of a suggestive linkage signal at the three known RLS susceptibility loci is indicative of further locus heterogeneity of this frequent disorder and encourages further studies to unveil the genetic causes of RLS.

Segregation Analysis of Restless Legs Syndrome: Possible Evidence for a Major Gene in a Family Study Using Blinded Diagnoses

Objective: The objective of this study was to ascertain the most likely inheritance pattern of restless legs syndrome (RLS) using segregation analysis. Methods: Probands were RLS patients presenting to the Neurology and Sleep clinics of the Johns-Hopkins Bayview medical center with willing first and second degree relatives. Blinded diagnosis was made in those who exhibited the four diagnostic features of RLS. Analysis was performed on RLS as a dichotomous trait and considering age of onset models on 590 phenotyped subjects from 77 pedigrees. Results: All non-genetic models were rejected considering RLS as a dichotomous trait. A single locus Mendelian dominant model with gender as a covariate had best fit with allele frequency of 0.077 and complete penetrance. RLS frequency in non-carrier subjects was estimated to be 0.14. Two underlying distributions of age of onset, with a possible dichotomy at 26.3 years, were identified. Contrary to the results for RLS as a dichotomous trait, age of onset models did not indicate single major gene inheritance. Conclusion: This segregation analysis suggests that the pattern of segregation is consistent with that of a single major locus, when RLS is treated as a dichotomous trait without considering age of onset. The high rate of phenocopies matches known population frequencies and taken with significant residual familial effects and the lack of evidence for a major gene controlling age of onset, indicates that non-genetic causes of RLS may exist and RLS is a complex disorder.

Physostigmine for the Acute Treatment of Restless Legs Syndrome

We present a case report of an acute episode of restless legs syndrome that interfered with the performance of a diagnostic imaging procedure of the cervical spine. The patient had a 19-yr history of restless leg syndrome with periodic limb movements during sleep. Treatment with additional sedation and opioids did not alleviate the leg movements. IV administration of 1 mg of physostigmine eradicated all extraneous leg motion.

Secondary causes of restless legs syndrome in older people

Secondary causes of restless legs syndrome (RLS) have been reported to be more common in those with late-onset RLS. However, 'late-onset' in previous studies was defined as onset after 45 years. To determine the prevalence of secondary causes of RLS and the relationship between aetiological factors and age of symptom onset in an older population. Prospective study conducted over a 5-year period. 80 consecutive non-related patients diagnosed with RLS. Patients were assessed according to a standard protocol. Age at symptom onset, severity of symptoms, neurological findings and laboratory tests were examined. Iron deficiency (serum ferritin <50 ng/ml) was present in 22% of patients with onset before 50 years, 39% of those with onset at 50 to 64 years and 58% in those with onset after 64 years (P = 0.009). Clinical neuropathy was also more common in older-onset patients (P = 0.08). Family history was positive in 39%, 23% and 8% of these groups, respectively (P = 0.008). Secondary causes of RLS become more common and a positive family history less common with increased age of symptom onset.

Computerized movement analysis and beta-CIT-SPECT in patients with restless legs syndrome

Considering the positive effect of dopaminergic treatment on Restless Legs Syndrome (RLS), it has been suggested that the cause of RLS may be linked to central dopaminergic dysfunction. As problems of alternating movements can result from a failure in the dopaminergic system, we used a movement analysis system to analyse this and in-parallel, performed [123I]beta-CIT-SPECT to investigate signs of dopaminergic dysfunction in patients with RLS. In 10 patients with idiopathic RLS, we conducted a three-dimensional computerized ultrasound-based movement analysis before a single dose of levodopa (L-dopa) was given and 90 minutes after the L-dopa challenge. In 6 of the 10 RLS patients, the striatal dopamine transporter system was studied with [123I]beta-CIT-SPECT. We did not observe any significant change in the movement pattern with the computerized movement analysis and no significant effect of L-dopa on the movement. We did not detect any significant differences between patients and normal controls regarding beta-CIT-signals in putamen or caudate nucleus, respectively. There was, however, a slight but significant change regarding the relative [123I]beta-CIT-SPECT binding in the putamen vs. the caudate nucleus. We conclude that the methods used could not detect any definite signs of changed central dopaminergic function in patients with RLS.

Presynaptic dopaminergic function in patients with restless legs syndrome: are there common features with early Parkinson's disease?

The cause of restless legs syndrome (RLS) is unknown, but an involvement of the dopaminergic system and a possible relation to Parkinson's disease (PD) is suggested by the positive response to dopaminergic treatment. We imaged the striatal dopamine transporter with [(123)I] N-(3-iodopropen-2-yl)-2beta-carbomethoxy-3beta-(chloro-phenyl) tropane ([(123)I]IPT) and single-photon emission computed tomography (SPECT) in 28 RLS patients, and compared the results with transporter binding in 29 patients with early PD and 23 age-matched controls. No difference in IPT binding was found between RLS patients and controls. IPT binding was correlated significantly with age in RLS patients and controls, whereas there was no relation with the duration of symptoms or severity of RLS. PD patients presented significant lower presynaptic IPT binding ipsi- and contralateral to the affected body side compared with RLS patients or controls. We found no common characteristics between RLS patients and patients with early PD detectable by dopamine transporter SPECT. Our results do not strengthen an identical pathophysiologic pathway between RLS and PD on the level of nigrostriatal presynaptic terminal function.

Restless legs syndrome in blood donors

Background and purpose Restless legs syndrome (RLS) may be a cause of significant sleep disturbance. In a Swedish survey, the prevalence of RLS has been estimated to be 5.8% among men and 11.4% among women. Blood donation may result in iron deficiency, which is hypothesized to be one substantial cause of RLS. Patients and methods Nine hundred and forty-six (618 men, 328 women) consecutive blood donors aged 18–64 years, who attended a blood donation unit in mid-Sweden, answered a questionnaire that included questions about sleep habits. Frequency of blood donation was recorded and intake of iron tablets was assessed. Red blood cell distribution width (RDW) was also recorded. The value of RDW increases in relation to iron deficiency. Results RLS affected 14.7% of male and 24.7% of female blood donors. The mean intake of iron among the blood donors after each blood donation was only 781 mg, although the recommended intake is 2000 mg. Among the women, 7.4% presented an RDW of >14.5%, which strongly indicates iron deficiency. In this group of women, 37.5% were affected by RLS. The female RLS-sufferers were more affected than the female non-RLS subjects by problems initiating sleep ( P=0.006), maintaining sleep ( P<0.0001) and were also less refreshed upon awakening ( P<0.001). Results This study showed that RLS was common among female blood donors. Women with RLS were more iron-deficient than those without and were affected by impaired sleep.

A crossover study of gabapentin in treatment of restless legs syndrome among hemodialysis patients

Restless legs syndrome (RLS) is a common entity affecting hemodialysis patients. Although the cause of RLS remains unclear, a number of therapies have been used successfully to treat the disorder. Gabapentin is an anticonvulsant shown to alleviate symptoms of RLS in two small studies of nonhemodialysis patients. Because it is excreted renally, gabapentin has a long half-life among hemodialysis patients and may be advantageous if proven effective. We conducted a randomized, double-blind, placebo-crossover study of gabapentin in the treatment of RLS among a population of hemodialysis patients. Sixteen patients identified with RLS were randomized to either gabapentin or placebo. After 6 weeks of treatment with 200 to 300 mg of gabapentin after each hemodialysis session, patients' RLS was reassessed. After a 1-week washout period, patients were switched from gabapentin to placebo or placebo to gabapentin. After another 6 weeks, patients' RLS was assessed again. Patient data were analyzed using both parametric and nonparametric means. Thirteen of the 16 original patients completed the study. Two patients dropped out because of lethargy (believed to be secondary to gabapentin), and 1 patient died secondary to myocardial infarction. Eleven patients responded to gabapentin, but not placebo (P < 0.01). One patient responded to both, and 1 patient responded to placebo, but not gabapentin. Gabapentin is an effective treatment for RLS in hemodialysis patients. © 2001 by the National Kidney Foundation, Inc.