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Anxiety and depression are common causes of insomnia, but they are not the only causes. Neurological disorders such as restless legs syndrome and periodic limb movement disorder are also common. A conceptual model of sleep and wakefulness helps to explain different kinds of insomnia.
BACKGROUND AND PURPOSE: Periodic limb movement disorder (PLMD) is frequently accompanied by awakenings or signs of EEG arousal. However, it is matter of debate whether EEG arousals trigger leg movements or both EEG arousal and leg movements are separate expressions of a common pathophysiological mechanism. Previous studies showed that cardiac and cerebral changes occur in association with periodic limb movements (PLMs), and that a combining increase in delta activity and in heart rate (HR) occurs before the onset of PLMs. PATIENTS AND METHODS: This paper presents some preliminary data, obtained from a sample of 5 subjects with PLMD not associated to restless legs syndrome. To describe the temporal pattern of cardiac and EEG activities changes concomitant with PLMs in NREM sleep we used time frequency analysis technique. RESULTS: PLM onset is heralded by a significant activation of HR and delta activity power, beginning 4.25 and 3 s respectively before PLMs onset, with PLMs onset and arousal onset falling together. DISCUSSION: Delta and HR variations herald PLMs and activation of fast EEG frequencies. Such a stereotyped pattern is common in PLMs and in spontaneous or stimuli-induced arousals. Moreover a similar pattern seems to encompass the CAP phenomenon. The whole of these phenomena can be linked to the activity of a common brainstem system, which receives peripheral inputs, regulating the vascular, cardiac and respiratory activities and synchronizing them to cortical oscillations of EEG.
OBJECTIVE: To test the variations in cerebral motor excitability in patients with primary restless legs syndrome (RLS) by using electrophysiological techniques. In RLS patients periodic legs movements (PLMs) in sleep and wake have been described and it is hypothesised that PLMs result from a sleep-related disinhibition of descending central motor inhibitory pathways. Moreover, in primary RLS, these modifications are still debated. METHODS: In 15 patients with primary RLS, transcranial magnetic stimulation (TMS) was carried out using several paradigms, particularly paired pulse TMS with short interstimulus intervals (ISI) in abductor digiti minimi (ADM) and tibialis anterior (TA) muscles. RESULTS: Short ISI paired TMS showed a significant decrease in inhibition and increase in facilitation in ADM muscles. This result was even more evident in TA muscles of patients as compared to the controls and these modifications were more evident in the limbs which were more affected by PLM. Moreover, intracortical (corticocortical) inhibition (ICI) and intracortical facilitation (ICF) unchanged their biphasic time course. CONCLUSIONS: In our study the changes in short paired-pulse ICI and ICF revealed the presence of an altered excitability of central motor pathways, with good correlation with asymmetric distribution of symptoms.
BACKGROUND AND PURPOSE: Micro-arousals (MA) are commonly considered as sleep components reflecting sleep fragmentation. However, their elucidation is time-consuming, with considerable inter-observer variability. The aim of our study was to investigate the usefulness of a sleep fragmentation index (SFI) to detect sleep disruption in a large sample of patients. PATIENTS AND METHODS: Five-hundred ninety-eight polysomnographic studies made in controls and patients were examined. The SFI was calculated as the total number of awakenings and sleep stage shifts divided by total sleep time. RESULTS: In the whole group a significant correlation was found between the SFI and the MA index (MAI) (P<0.001) with good agreement across a wide range of values. When patients were stratified according to final diagnosis a significant relation was noted for patients with insomnia (P<0.001), parasomnia (P<0.001), circadian schedule disorders (P<0.001) and sleep related breathing disorders (P< 0.001). Lower values were found in controls (P<0.01) and in patients with periodic limb movement disorder and/or restless legs syndrome (P<0.05). In 111 patients having two consecutive recording nights, a good reproducibility was present with no differences between nights (P=ns) and with significant correlation (P<0.001). CONCLUSIONS: The SFI seems to be an accurate, reproducible and easy method to detect sleep fragmentation in patients with sleep disorders. Further studies are needed to validate the usefulness of this tool in clinical practice.
BACKGROUND: Progressive systemic sclerosis (SSc) is a connective tissue disease characterized by endothelial lesions and fibrosis of the skin and other organs. Patients' quality of life and life expectancy are determined by the intensity of pulmonary, esophageal, cardiac, and renal involvement. Neurological involvement was considered to be rare, but increasing evidence indicates that peripheral and autonomic neuropathies commonly occur. Conditions seen with SSc, such as pulmonary fibrosis and gastro-esophageal reflux, have the potential to affect sleep. No systematic assessment of sleep-related problems associated with this disorder has been performed. MATERIAL AND METHODS: An all-night polysomnogram and a clinical interview blinded to sleep status were obtained for 27 consecutive SSc patients. Sleep data were compared to age adjusted published normative values. Correlations were determined for sleep and clinical data. RESULTS: Patients with SSc had a reduced sleep efficiency (SE) (mean+/-SD: 82+/-12.3%) and rapid eye movement sleep (13.1+/-5.6%) and increased arousal index (26.1+/-13.0) and slow wave sleep (25.7+/-9.7%). The periodic leg movement index (PLMI) exceeded 5/h in 13 patients (48%) and 25/h in seven patients. Six patients had restless legs syndrome (RLS). Significant disordered breathing was absent. The RLS patients showed a greater arousal index than all other patients. PLMI was correlated with SE for RLS but not for non-RLS patients. Esophageal dyskinesia, dyspnea, and RLS were significantly associated with poor sleep. CONCLUSION: Patients with SSc have significant disturbance of their sleep. Esophageal dyskinesia and dyspnea, which are common complications of SSc, were commonly associated with indices of sleep disruption. RLS but not sleep apnea appears to have an increased prevalence in SSc.
Actigraphy is a method used to study sleep-wake patterns and circadian rhythms by assessing movement, most commonly of the wrist. These evidence-based practice parameters are an update to the Practice Parameters for the Use of Actigraphy in the Clinical Assessment of Sleep Disorders, published in 1995. These practice parameters were developed by the Standards of Practice Committee and reviewed and approved by the Board of Directors of the American Academy of Sleep Medicine. Recommendations are based on the accompanying comprehensive review of the medical literature regarding the role of actigraphy, which was developed by a task force commissioned by the American Academy of Sleep Medicine. The following recommendations serve as a guide to the appropriate use of actigraphy. Actigraphy is reliable and valid for detecting sleep in normal, healthy populations, but less reliable for detecting disturbed sleep. Although actigraphy is not indicated for the routine diagnosis, assessment, or management of any of the sleep disorders, it may serve as a useful adjunct to routine clinical evaluation of insomnia, circadian-rhythm disorders, and excessive sleepiness, and may be helpful in the assessment of specific aspects of some disorders, such as insomnia and restless legs syndrome/periodic limb movement disorder. The assessment of daytime sleepiness, the demonstration of multiday human-rest activity patterns, and the estimation of sleep-wake patterns are potential uses of actigraphy in clinical situations where other techniques cannot provide similar information (e.g., psychiatric ward patients). Superiority of actigraphy placement on different parts of the body is not currently established. Actigraphy may be useful in characterizing and monitoring circadian rhythm patterns or disturbances in certain special populations (e.g., children, demented individuals), and appears useful as an outcome measure in certain applications and populations. Although actigraphy may be a useful adjunct to portable sleep apnea testing, the use of actigraphy alone in the detection of sleep apnea is not currently established. Specific technical recommendations are discussed, such as using concomitant completion of a sleep log for artifact rejection and timing of lights out and on; conducting actigraphy studies for a minimum of three consecutive 24-hour periods; requiring raw data inspection; permitting some preprocessing of movement counts; stating that epoch lengths up to 1 minute are usually sufficient, except for circadian rhythm assessment; requiring interpretation to be performed manually by visual inspection; and allowing automatic scoring in addition to manual scoring methods.
This article addresses the history, diagnostic criteria, pharmacotherapy, non-pharmacological symptom management, and coping mechanisms for idiopathic restless legs syndrome (RLS). The prevalence and treatment for uremia-associated RLS, as described in the literature, and special consideration of the problems of the dialysis patient with RLS will be addressed. The associated sleep disorder, periodic limb movements of sleep (PLMS), will also be reviewed.
First results from studies in healthy subjects with the beta-carbolines ZK 91 296, ZK 95 962 and ZK 93 426 are reviewed. ZK 91 296 and ZK 95 962, characterized as partial benzodiazepine agonists in preclinical research, were unable to induce some typical benzodiazepine effects like sedation when administered intravenously in high doses. ZK 95 962, reported to be effective in photoepileptic patients, was able to reverse lormetazepam-induced sleep as documented by EEG-parameters. The benzodiazepine receptor antagonist ZK 93 426 dose-dependently elicited alertness, restlessness and mild apprehension--symptoms opposite those known for the benzodiazepines. The activating effect of ZK 93 426 was confirmed by the results from e.g., self-rating scales and the logical reasoning test. In another placebo-controlled study comparing the effects of ZK 93 426 alone and in combination with lormetazepam vigilosomnograms obtained after ZK 93 426 alone clearly confirmed the activating effect. In combination with lormetazepam ZK 93 426 was able to reverse the benzodiazepine induced sleep. The attenuation of benzodiazepine effects was also evident from multiple sleep latency tests. Our results support findings from animal experiments which classify these beta-carbolines as benzodiazepine receptor ligands with partial agonist and antagonist properties. beta-Carbolines may prove to be beneficial drugs in the treatment of anxiety, convulsions and diseases with an impairment of cognitive functions as well as in the reversal of unwanted benzodiazepine effects.
The prevalence of restless legs syndrome (RLS) in various regions in the world has been estimated between 2.5 and 29%. For The Netherlands these figures are not known. Our observational and cross-sectional study was performed to estimate the prevalence of RLS in The Netherlands. A cross-sectional survey by postal questionnaire was carried out through a general practice in a small town in which one general practice serves 93% of the population. All men and women aged 50 years and older were invited to fill out the questionnaire on leg movements, quality of sleep and daytime symptoms. A total of 1485 (88.2%) persons returned their questionnaire and 1437 (85.4%) patients answered the questions on leg movements. A total of 102 (7.1%) inhabitants answered positively to the questions on leg movements and probably have RLS. The prevalence was higher in women and increased with age. People who complain of RLS have significantly more complaints of disturbances in initiating and maintaining sleep, sleepiness, tiredness during the day and less refreshing sleep. RLS is common in The Netherlands with an estimated prevalence of 7.1% in the population over 50 years of age.
OBJECTIVE: To investigate the efficacy and safety of levodopa plus benserazide in the treatment of restless legs syndrome (RLS), in terms of the frequency of periodic limb movements (PLMs), objective and subjective criteria of sleep, onset of action, and withdrawal effects. DESIGN: A randomized, double-blind, placebo-controlled, multicenter, crossover trial, with two 4-week treatment periods. SETTING: Outpatient units of three specialist centers in Germany. PATIENTS: Eligible patients had to fulfill the diagnostic criteria of the International RLS Study Group and have sleep disturbances and PLMs during sleep shown on polysomnography at screening. Thirty-five patients were recruited, of whom 32 (13 men, 19 women) completed the study. INTERVENTIONS: Patients received a single dose of standard-release levodopa/benserazide 100/25 mg or placebo at bedtime each night for 4 weeks, before crossing over to receive the alternative treatment for a further 4 weeks; the dose could be doubled if required. The average dosages were 159 +/- 31 mg of levodopa and 1.56 +/- 0.29 capsules of placebo. RESULTS: Levodopa/benserazide significantly reduced the number of PLMs per hour (p<0.0001), increased the time in bed without limb movements (p<0.0001), and improved subjective quality of sleep (p=0.0004). The onset of action was rapid after the first dose, and full efficacy was achieved within the first few days of therapy; these improvements disappeared immediately when treatment was discontinued. Levodopa/benserazide treatment was well tolerated and safe. CONCLUSIONS: Levodopa/benserazide is effective and safe in the treatment of RLS. Objective and subjective measures of sleep improved rapidly after the first dose. RLS symptoms recurred immediately after treatment was discontinued.
STUDY OBJECTIVE: To review evidence on the association between restless legs syndrome (RLS) and attention-deficit/hyperactivity disorder (ADHD), to discuss the hypothetical mechanisms underlying this association, and to consider the potential interest for common pharmacologic treatments of RLS and ADHD when co-occurring. METHOD: A PubMed search. RESULTS: In clinical samples, up to 44% of subjects with ADHD have been found to have RLS or RLS symptoms, and up to 26% of subjects with RLS have been found to have ADHD or ADHD symptoms. Several mechanisms may explain this association. Sleep disruption associated with RLS might lead to inattentiveness, moodiness, and paradoxical overactivity. Diurnal manifestations of RLS, such as restlessness and inattention, might mimic ADHD symptoms. Alternatively, RLS might be comorbid with idiopathic ADHD. Subjects with RLS and a subset of subjects with ADHD might share a common dopamine dysfunction. Limited evidence suggests that some dopaminergic agents, such as levodopa/carbidopa, pergolide, and ropinirole, may be effective in children with RLS associated with ADHD symptoms. CONCLUSIONS: Although still limited, evidence from clinical studies demonstrates an association between RLS and ADHD or ADHD symptoms. Further clinical studies using standard criteria and procedures are needed to better estimate the degree of association. Epidemiologic studies are required to assess the relationship between ADHD and RLS symptoms in nonclinical samples. Further investigations should address the mechanisms underlying the relationship between RLS and ADHD. Several dopaminergic agents seem to be promising treatment for RLS associated with ADHD symptoms. To date, however, the absence of randomized and blinded controlled studies does not allow evidence-based recommendations.
Insomnia and depression are widespread diseases causing deterioration of life's quality and increasing morbidity and mortality of cardiovascular diseases. Both of them and certain antidepressants adversely affect physiological structure of sleep, while others restore it. The latter drugs must be preferred in therapy of depression accompanying insomnia, and some of them may be effective in treatment of insomnias without depression. Most antidepressants cause REM-reduction, generally with increased serotonin-function. Selective H1-antagonists readily induce sleep, and also the inhibition of cholinergic neurons in the general arousal networks promotes sleep. Sleep continuity is improved by the rise of synaptic level of serotonin. Among tricyclic antidepressants trimipramine and amitriptyline are the best to improve sleep. However, the former has low antidepressant effect and the latter has many adverse side effects. Selective serotonin reuptake inhibitors, except paroxetine, improve sleep only at the time and to the extent of restoring depression. Paroxetine has beneficial effect on sleep at the beginning of the treatment. Mirtazapine is the first-line sleep promoter among atypical antidepressants, however, its effect on increasing appetite markedly limits its application. Trazodone causes hangover, and mianserin may induce restless legs. Insomnias without depression demand lower dose of antidepressants than depression.
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One hundred thirty-three cases of restless legs syndrome (RLS), diagnosed with criteria recently formulated by an international study group, were studied by questionnaire and with all-night polysomnographic recordings. Results show that RLS starts at a mean age of 27.2 years and before age 20 in 38.3% of patients. Symptoms often appear in one leg only and also involve upper limbs in about half of all cases. Most patients (94%) report sleep-onset insomnia or numerous nocturnal awakenings due to RLS symptoms. A strong relationship was found between these complaints and polysomnographic findings; increasing sleep latency and number of awakenings and decreasing sleep efficiency were associated with worsening symptoms. Periodic leg movements in sleep (index > 5 movements/h sleep) were found in 80.2% of patients. This study shows that this percentage is increased when 2 recording nights are considered (most severe score). Eighty patients of 127 (63%) reported the presence of RLS in at least one of their first-degree relatives. In these families, 221 of 568 first-degree relatives (39%) were reported by the patients to be affected with RLS.
Seventy-nine pairs of same-sex twins were examined at the age of three years at a municipal clinic and their mothers were interviewed to assess the twins' current and past behaviours. The zygosity was determined after the interview by fingerprints and/or bloodtyping in the majority of cases. The following significant differences in concordance between monozygotic and dizygotic twins were found: fear of strangers during observation at the clinic; marked fear of strangers in the first year of life; whether or not the child was startled by sudden noises during infancy; whether or not the child was able to sleep alone at three years without a parent sitting nearby; susceptibility to motion sickness; nocturnal enuresis; short attention span or restlessness during the test.
There is a genetic contribution to the idiopathic restless legs syndrome (iRLS). An autosomal dominant mode of inheritance is suspected, but as yet no gene has been identified. To assess the frequency and characteristics of the hereditary restless legs syndrome (RLS) in comparison to those of non-hereditary RLS, we analysed the clinical data of 300 RLS patients. All 300 patients diagnosed as RLS according to the criteria of the International RLS Study Group were examined using a standard questionnaire covering demographic data, family history, clinical symptoms, subjective sleep disturbances and course of the disease. In all patients a complete neurological examination was performed, and in selected cases electrophysiological examinations and polysomnographic studies. Family history was rated as definitely positive when at least one first-degree relative was examined and classified as RLS according to the criteria by one of the authors. If it proved impossible to contact family members to verify reports of a family history, the patients were classified as only having a "possible positive family history." 232 of the 300 patients had iRLS and 68 secondary RLS due to uremia (uRLS). 42.3% of the patients with iRLS and 11.7% of those with uRLS were classified as having "definite positive" hereditary RLS, with a further 12.6% of iRLS patients and 5.8% of uRLS patients as having "possible positive" hereditary RLS. Patients with definite hereditary RLS were significantly younger at the age of onset than those with a negative family history (35.45 vs. 47.17 years, p < 0.05). The clinical characteristics of the disease were similar in both groups, except that women with hereditary RLS experienced a worsening of symptoms during pregnancy (19.1% vs. 2.6%, p < 0.05). Our study shows that patients with hereditary RLS may experience an earlier onset of the disease. Hereditary and non-hereditary RLS present with similiar clinical signs and symptoms.
Efficacy and safety of the dopamine agonist rotigotine (RTG) was investigated in patients with moderate to severe idiopathic restless legs syndrome (RLS), including daytime symptoms. Three fixed doses of rotigotine (1.125 mg, 2.25 mg, and 4.5 mg) and placebo were applied by patches (size, 2.5 cm2 per 1.125 mg) in a double-blind, randomized, parallel-group, multicenter, 1-week, proof-of-principle trial. The primary efficacy measure was the total score on the International Restless Legs Syndrome Scale (IRLS). Additionally, the RLS-6 scale, the Clinical Global Impressions (CGI), and a sleep diary were used. Of 68 enrolled patients, 63 (mean age, 58+/-; 9 years; 64% women) were randomly assigned. RLS severity improved related to dose by 10.5 (1.125 mg RTG/die; P = 0.41), 12.3 (2.25 mg RTG/die; P = 0.18), and 15.7 points (4.5 mg RTG/die; P < 0.01) on the IRLS compared to placebo (8 points). According to the RLS-6 scales, daytime symptoms significantly improved with all rotigotine doses. The CGI items supported the favorable efficacy of the 4.5-mg dose. Skin tolerability of the patches and systemic side effects were similar between rotigotine and placebo. This pilot study suggests that continuous delivery of rotigotine by means of a patch may provide an effective and well-tolerated treatment of RLS symptoms both during night and day.
STUDY OBJECTIVES: evaluation of shift-work effect on sleepiness, sleep disorders, and sleep-related accidents in a population of police officers. DESIGN: Aquestionnaire-based survey was used to gather information on age and physical characteristics, working conditions, sleep problems, and accidents. Sleepiness was measured by the Epworth Sleepiness Scale (ESS) while the presence of sleep disorders was evaluated by a score (SDS) drawn from indicators of insomnia, breathing disorders, periodic limb movements and restless legs syndrome, and hypersomnia. The effects of age, gender, body mass index, working conditions, and seniority on ESS, SD score, and accidents were analyzed by linear and logistic regression. SETTING: The self-administered questionnaires were filled in by police officers in the district of Genoa (Italy). PARTICIPANTS: 1,280 police officers: 611 shift workers (SW) and 669 non-shift workers (NSW). INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: The ESS score was not higher in SW than in NSW, while the SDS was significantly influenced by shift-work conditions and seniority in shift work. The occurrence of sleep-ascribed accidents was significantly increased in the SW group and related to the presence of indicators of sleep disorders. There was evidence for sleep disorders in 35.7% of SW and in 26.3% of NSW. CONCLUSIONS: Shift-work conditions and seniority may enhance sleep disorders and may favor sleep-related accidents, but they do not influence ESS score. Stressful conditions could cause sleepiness to be underestimated, or else they might overcome sleepiness. However, our data should alert occupational health physicians for the diagnosis and prevention of possible undetected intrinsic sleep disorders, which could possibly worsen shift workers' health and increase the risk of accidents.