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Restless legs syndrome and sleep problems in children and adolescents with insulin-dependent diabetes mellitus type 1.

The restless legs syndrome (RLS) occurs in adulthood with a prevalence of 5 to 10% and can be associated with diabetes mellitus. The prevalence in childhood, however, is unknown. We asked consecutive children with type 1 (insulin-dependent) diabetes mellitus as well as their parents and siblings about RLS according to a standardised questionnaire. Altogether, 46 patients (25 female, 12.0 +/- 3.7 years), 50 siblings (29 female, 12.3 +/- 5.5 years) and 75 parents (41 mothers, 40.4 +/- 5.1 years; 34 fathers, 42.5 +/- 5.3 years; 1.3 % with diabetes mellitus) were included. One patient (2.2%), one sibling (2.0%), and 14 parents (18.7%) were diagnosed as having RLS. Disturbances of sleep initiating, sleep maintenance and daytime tiredness were similar in patients and siblings. There was a significant association of higher HbA1c values (mean 7.7 +/- 2.2%) with sleep initiating problems. The mean dose of international units of insulin/kg body weight/day (0.79 +/- 0.26 IU) was not associated with the presence of RLS or sleep problems. To conclude, there seems to be no association of diabetes mellitus type 1 with RLS in children and adolescents. However, there is a relationship between diabetes and sleep disturbances and an optimally controlled diabetes mellitus might be an important factor for an improved sleep initiation.

Adolescent↗

Sleep laboratory studies in restless legs syndrome patients as compared with normals and acute effects of ropinirole. 2. Findings on periodic leg movements, arousals and respiratory variables.

The restless legs syndrome (RLS) is a common sensorimotor disorder which leads to severe sleep disturbances and showed a prevalence of 7.9% in our sleep laboratory. The aim of this study was to investigate periodic leg movements (PLM), arousal and respiratory variables in 12 untreated RLS patients and to measure the acute effects of 0.5 mg ropinirole, a nonergoline dopamine agonist, as compared with placebo. In the target variable PLM/h of total sleep time (PLM/h TST), RLS patients showed an increased value of 40/h (normal 0-5/h). Further, we found an increased number of PLM (368), PLM/h of time in bed (49/h), PLM/h of REM sleep (11), PLM/h of non-REM sleep (46) and PLM/h awake (61). The arousal index was also increased (32/h; normal 0-25/h), as were arousals due to PLM. In the confirmatory part of our descriptive data analysis, ropinirole 0.5 mg significantly improved, as compared with placebo, the index PLM/h TST by 75%. In the descriptive part, all the other PLM variables were improved as well. Arousals due to PLM decreased, while spontaneous arousals increased. Respiratory variables, which had a priori been in the normal range, showed a slight but significant improvement after the dopamine agonist. Thus, 0.5 mg ropinirole significantly improved the target variable PLM/h TST, along with objective and subjective sleep quality and morning noopsychic performance, as described in the preceding paper. Our data encourage further sleep studies including all above-mentioned variables in a larger group of RLS/PLM during sleep patients as well as long-term efficacy trials.

Adult↗

Abnormal movements in sleep as a post-polio sequelae.

Nearly two-thirds of polio survivors report abnormal movements in sleep, with 52% reporting that their sleep is disturbed by these movements. Sleep studies were performed in seven polio survivors to document objectively abnormal movements in sleep. Two patients demonstrated generalized random myoclonus, with brief contractions and even ballistic movements of the arms and legs, slow repeated grasping movements of the hands, slow flexion of the arms, and contraction of the shoulder and pectoral muscles. Two other patients demonstrated periodic movements in sleep with muscle contractions and ballistic movements of the legs, two had periodic movements in sleep plus restless legs syndrome, and one had sleep starts involving only contraction of the arm muscles. Abnormal movements in sleep occurred in Stage II sleep in all patients, in Stage I in some patients, and could significantly disturb sleep architecture even though patients were totally unaware of muscle contractions. Poliovirus-induced damage to the spinal cord and brain is presented as a possible cause of abnormal movements in sleep. The diagnosis of post-polio fatigue, evaluation of abnormal movements in sleep, and management of abnormal movements in sleep using benzodiazepines or dopamimetic agents are described.

Electromyography↗

Sleep disturbances and excessive daytime sleepiness in Parkinson disease: an overview.

Sleep disturbances are frequent in Parkinson disease. These disorders can be broadly categorized into those that involve nocturnal sleep and excessive daytime sleepiness. The disorders that are often observed during the night in PD include sleep fragmentation that may be due to recurrent PD symptoms, sleep apnea, Restless Leg Syndrome/ periodic limb movements and REM sleep behavior disorder. Excessive daytime sleepiness is also a common occurrence in PD. EDS can arise from several etiologies, and patients may have more than one etiology responsible. The causes of EDS include nocturnal sleep disorder with sleep deprivation and resulting daytime somnolence, the effect of drugs used to treat PD, and possibly neurodegeneration of central sleep/wake areas. Appropriate diagnosis of the sleep disturbance affecting a PD patient can lead to specific treatments that can consolidate nocturnal sleep and enhance daytime alertness.

Animals↗

[Diagnosis and classification of sleep disorders].

When sleep was recognized as an active process which is regulated by the interaction of homeostatic and circadian systems a new understanding of sleep disturbances set in, and sleep medicine developed as a new medical speciality. An internationally recognized classification system was developed which allows to diagnose the different sleep disturbances reliably. Sleep disorders comprise (a) dysregulations of the sleep-wake system (insomnias, hypersomnias, narcolepsy, parasomnias), (b) sleep associated disturbances of functional systems (for example sleep apnea, restless legs syndrome), (c) disturbances of the circadian sleep-wake rhythm, and (d) sleep disturbances in association with other organic or psychiatric illnesses. The present contribution shows the diagnostic procedures for four main sleep disorders, namely insomnia, obstructive sleep apnea (OSAS), restless legs syndrome (RLS), and narcolepsy.

Circadian Rhythm↗

[Restless legs syndrome and periodic leg movements during sleep in patients with sleep apnea--a therapeutic problem?].

Restless-legs syndrome and periodic movements during sleep are associated with sleep apnoea syndrome. Similar to sleep apnoea syndrome, restless-legs syndrome and periodic movements during sleep may cause severe hyposomnia and hypersomnia. Exact diagnosis may partly fail in severe obstructive sleep apnoea syndrome if only cardiorespiratory polygraphy is performed. Simultaneous videorecordings and EMG of mm. tibialis ant. ensure diagnosis. Therapeutic regime may be difficult due to failure or side effects, however. We report on our experience in an one-year follow-up of 12 patients with sleep apnoea syndrome and restless-legs syndrome and/or periodic movements during sleep. Despite adequate interdisciplinary initiation of therapy and monitoring, these patients are often subject to therapy changes, failures or side effects. There was no correlation between jerks and the complaints of the patients.

Aged↗

Sleep and circadian phase in a ship's crew.

Numerous factors influence the increased health risks of seamen. This study investigated sleep (by actigraphy) and the adaptation of the internal clock in watch-keeping crew compared to day workers, as possible contributory factors. Fourteen watch keepers, 4 h on, 8 h off (0800-1200/2000-2400 h, 1200-1600/2400-0400 h, 1600-2000/0400-0800 h) (fixed schedule, n = 6; rotating by delay weekly, n = 8), and 12 day workers participated during a voyage from the United Kingdom to Antarctica. They kept daily sleep diaries and wore wrist monitors for continuous recording of activity. Sleep parameters were derived from activity using the manufacturer's software and analyzed by repeated-measures ANOVA using SAS 8.2. Sequential urine samples were collected for 48 h weekly for 6-sulphatoxymelatonin measurement as an index of circadian rhythm timing. Individuals working watches of 1200-1600/2400-0400 h and 1600-2000/0400-0800 h had 2 sleeps daily, analyzed separately as main sleep (longest) and 2nd sleep. Main sleep duration was shorter in watch keepers than in day workers (p < 0.0001). Objective sleep quality was significantly compromised in rotaters compared to both day workers and fixed watch keepers, the most striking comparisons being sleep efficiency (percentage desired sleep time spent sleeping) main sleep (p < 0.0001) and sleep fragmentation (an index of restlessness) main sleep (p < 0.0001). The 2nd sleep was substantially less efficient than was the main sleep (p < 0.0001) for all watch keepers. There were few significant differences in sleep between the different watches in rotating watch keepers. Circadian timing remained constant in day workers. Timing of the 6-sulphatoxymelatonin rhythm was later for the watch of 1200-1600/2400-0400 h than for all others (1200-1600/2400-0400 h, 5.90 +/- 0.85 h; 1600-2000/0400-0800 h, 1.5 +/- 0.64 h; 0800-1200/ 2000-2400 h, 2.72 +/- 0.76 h; days, 2.09 +/- 0.68 h [decimal hours, mean +/- SEM]: ANOVA, p < 0.01). This study identifies weekly changes in watch time as a cause of poor sleep in watch keepers. The most likely mechanism is the inability of the internal clock to adapt rapidly to abrupt changes in schedule.

Adult↗

Familial restless legs with periodic movements in sleep: electrophysiologic, biochemical, and pharmacologic study.

Restless legs syndrome was present in nine members of a family over a span of five generations. In three subjects, the diagnosis was confirmed by all-night sleep recordings and concomitant EMG. Two of these three subjects also had periodic movements in sleep. The frequency of leg movements decreased from wakefulness to stages 1 and 2 non-REM sleep. There was an increase of free dopamine and homovanillic acid in CSF of the propositus. Clonazepam effectively controlled restless legs in the propositus and his mother.

Adult↗

Sleep laboratory diagnosis of restless legs syndrome.

Polysomnographic recordings and the Suggested Immobilization Test (SIT) are frequently used to support the clinical diagnosis of restless legs syndrome (RLS). The present study evaluated the discriminant power of 5 different parameters: (1) index of periodic leg movements during sleep (PLMS), (2) index of PLMS with an associated microarousal (PLMS-arousal), (3) index of PLM during nocturnal wakefulness (PLMW), (4) SIT PLM index and (5) mean subjective leg discomfort score during the SIT (SIT MDS) in 100 patients with idiopathic RLS and 50 healthy control subjects. Both groups differed significantly on each parameter studied. Furthermore, while the SIT PLM, the PLMS and the PLMS-arousal indices revealed a poor ability to discriminate patients from controls, the PLMW index and the MDS both showed high sensitivity (87 +/- 7 and 82 +/- 8, respectively) and specificity (80 +/- 11 and 84 +/- 10, respectively) for diagnosing RLS. The combination of these 2 parameters correctly classified 88% of all subjects with a sensitivity of 82% and a specificity of 100%.

Adult↗

Akathisia, restless legs and periodic limb movements in sleep in Parkinson's disease.

Restless legs syndrome (RLS) symptoms are often reported in Parkinson's disease (PD), but prevalence studies of RLS in PD are few and the results are inconsistent. In addition, clinical overlapping between RLS, "wearing-off"-related lower limb discomfort and restlessness, and akathisia complicate the clinical assessments of true RLS in PD. Underlying pathophysiology potentially shared by RLS and PD is mainly suggested by similarities in treatment response. Functional imaging studies in RLS are still inconclusive, although some authors have found subtle deficits in nigrostriatal terminal function. Long-term prospective studies of RLS cohorts will clarify whether or not RLS is associated with an increased risk for development of PD.

Akathisia, Drug-Induced↗

Pergolide-associated 'sleep attacks' in a patient with restless legs syndrome.

The occurrence of irresistible sleep episodes ('sleep attacks') has been noted in patients with Parkinson's syndrome treated with dopa-agonists. This is the first report of 'sleep attacks' in a patient with restless legs syndrome in whom treatment with pergolide was reduced from 2 to less than 1 mg/day. 'Sleep attacks' were accompanied by a reduced mean sleep latency of 5 min and 20 s (without sleep onset REM periods) on a multiple sleep latency test. 'Sleep attacks' disappeared when pergolide was tapered off and substituted with pramipexol. The appearance of 'sleep attacks' as a 'withdrawal' effect of pergolide is consistent with a wakefulness-promoting action of postsynaptic dopaminergic receptors at higher doses of dopamine agonists.

Journal Article↗

Correlation between rating scales and sleep laboratory measurements in restless legs syndrome.

OBJECTIVES: The aim of this study was to test the external validity of the International Restless Legs Scale (IRLS) by assessment of the correlation between IRLS scores and objective measures of severity such as polysomnography (PSG) and Suggested Immobilization Test (SIT). DESIGNS: Correlation analysis between rating scales for RLS (IRLS and Johns Hopkins RLS Scale--JHRLSS) and sleep laboratory measurements in untreated RLS patients. METHODS: The study included 30 untreated patients diagnosed with RLS according to the criteria of the International RLS Study Group. Diagnostic procedures included physical exam, laboratory analysis, PSG and a nocturnal SIT. Statistical analysis was performed by means of Spearman's correlations and Kruskal-Wallis test. RESULTS: IRLS correlated significantly with Periodic Leg Movement of Sleep-index (PLMS), and PLMS-arousal index during PSG as well as with Periodic Leg Movement of Wakefulness (PLMW) during SIT (SIT-PLMW) (all r=0.4; p<0.01). There was no correlation between IRLS and the number of PLMW in PSG (PSG-PLMW) or any other sleep variable during PSG. Nor was any correlation found between IRLS scores and ferritin, age, duration of illness or any other clinical variables. CONCLUSIONS: This study represents the first demonstration of a correlation between IRLS and objective parameters of motor dysfunction such as PLMS-index or SIT. This finding is particularly relevant for the design of future clinical trials. Furthermore, the association between PLMS and SIT-PLMW supports the view that both PLMS and PLMW might share a common mechanism.

Adult↗

Sleep disturbance, stroke, and heart disease events: evidence from the Caerphilly cohort.

OBJECTIVE: To test the hypothesis that sleep disorders are relevant to the risk of ischaemic stroke and ischaemic heart disease events in older men. DESIGN: A cohort study. SETTING: The Caerphilly cohort, a representative population sample of older men in South Wales, UK. PARTICIPANTS: 1986 men aged 55-69 years completed a questionnaire on sleep patterns with help from their partners. This asked about symptoms of disturbed sleep: insomnia, snoring, restless legs, obstructive sleep apnoea, and about daytime sleepiness. During the following 10 years 107 men experienced an ischaemic stroke and 213 had an ischaemic heart disease event. MAIN RESULTS: Up to one third of the men reported at least one symptom suggestive of sleep disturbance, and one third reported daytime sleepiness. Compared with men who reported no such symptoms, the adjusted relative odds of an ischaemic stroke were significantly increased in men with any sleep disturbance, the strongest association being with sleep apnoea (relative odds 1.97; 1.26 to 3.09). The association with daytime sleepiness was not significant for stroke. Relations with ischaemic heart disease events were all raised in men with symptoms of sleep disturbance, but none was significant, other than daytime sleepiness (relative odds: 1.41; 1.04 to 1.92). There were no significant relations with blood pressure. CONCLUSION: The risk of an ischaemic stroke is increased in men whose sleep is frequently disturbed, and daytime sleepiness is associated with a significant increase in ischaemic heart disease events.

Aged↗

Breathing during sleep.

Hypoxaemia during the rapid eye movement phase of sleep is common in older healthy normal subjects over 55 years of age; the sleep apnoea syndromes--such as obstructive sleep apnoea, where oro-nasal airflow ceases for more than 10 seconds on many separate occasions throughout the night, due to failure of contraction of the genio-glossus muscle; "blue and bloated" patients with chronic bronchitis and emphysema, where profound nocturnal hypoxaemia is common in REM sleep, and is associated with further elevation of pulmonary arterial pressure; the overlap syndrome--where "blue and bloated" chronic bronchitis is associated with an obstructive sleep apnoea syndrome; and bronchial asthma, where hypoxaemia is associated with irregular breathing and possibly nocturnal bronchoconstriction. Although absolute recognition depends upon all night sleep studies, monitoring of ear oxygen saturation, breathing patterns, and EEG, the clinical features when awake can lead to suspicion of sleep hypoxaemia--as, for example, obesity and obstructive sleep apnoea with loud snoring and restlessness in sleep, hypoxaemia during wakefulness in the overlap syndrome, and nocturnal awakening with wheeze in bronchial asthma. Treatment depends on the cause, and may vary from weight loss and nasal continuous positive airway pressure in obstructive sleep apnoea, to nocturnal oxygen in "blue bloaters", a combination of these two in the overlap syndrome, and long acting bronchodilators such as slow release theophyllines in nocturnal asthma. Recognition and appropriate treatment of nocturnal hypoxaemia is an important new development in respiratory medicine.

Age Factors↗

Characterization of symptoms of sleep disorders in children with headache.

To investigate the prevalence of sleep disorders and their symptoms in children with headaches, 64 patients in the outpatient clinics of the University of Chicago Department of Pediatric Neurology were interviewed. Investigated disorders included excessive daytime sleepiness, narcolepsy, insomnia, sleep apnea, restlessness, and parasomnias. Unlike previous studies, subjects were compared with matched control patients by age and sex. Both headache and nonheadache groups completed a 111-item questionnaire detailing sleep symptoms and behaviors. It was found that children with headaches have a significantly higher prevalence of excessive daytime sleepiness, narcolepsy, and insomnia than children without headaches (P < 0.005), which is consistent with prior literature. A similar result was obtained in examining only migraines. However, we did not find a significantly higher prevalence of symptoms of sleep apnea, restlessness, and parasomnias, which contradicts previous literature. Also, the effect of medications taken by headache patients as a confounding factor was insignificant. Overall, pediatricians may find it beneficial to ask about daytime sleepiness, narcolepsy, and insomnia when treating a headache patient.

Case-Control Studies↗

Flupenthixol versus diazepam in the treatment of psychosomatic disorders: a double-blind, multi-centre trial in general practice.

In a Finnish general practice 120 patients with psychosomatic disorders, manifest as syndromes of tension headache, cardiac neurosis, dizziness or muscular tension, were randomly allocated to treatment over a 4-week period with either flupenthixol (1 to 2 mg per day) or diazepam (5 to 10 mg mg per day). The 4 syndromes and 12 associated symptoms (anxiety, fatigue, depression, pain, asthenia, muscle fatiguability, tension, dyspnoea, restlessness, palpitations, sleep disorders, and vertigo) were rated on a 4-point scale on entry, at 2 weeks and at 4 weeks. Both drugs reduced significantly the average total scores for syndromes and single symptoms after 2-weeks' treatment. Flupenthixol was the more effective in relieving fatigue and vertigo; diazepam in relieving headache, anxiety, tension, restlessness and sleep disturbance. Cardiac neurosis, palpitations and general muscular tension responded poorly to both drugs. After 4 weeks, relief of vertigo, pain and fatigue was more evident in the flupenthixol group, and of anxiety, tension and restlessness in the diazepam group. Side-effects were complained of at some stage by 17 patients in the flupenthixol group (9 of fatigue, 5 of sleep disturbance, 1 of constipation, 1 of extrapyramidal symptoms, and 1 of weight gain) and by 16 patients in the diazepam group (10 of fatigue, 4 of sleep problems and 2 of diarrhoea).

Adult↗

Ropinirole decreases periodic leg movements and improves sleep parameters in patients with restless legs syndrome.

STUDY OBJECTIVES: Polysomnographic study evaluating the efficacy of ropinirole for the treatment of patients with restless legs syndrome (RLS) suffering from periodic leg movements in sleep (PLMS). DESIGN: Double-blinded, placebo-controlled, parallel-group study. SETTING: 15 tertiary referral centers in the USA. PARTICIPANTS: 65 patients with RLS and PLMS. INTERVENTIONS: Ropinirole (0.25-4.0 mg per day) or placebo for 12 weeks. MEASUREMENTS AND RESULTS: Data from 59 patients were included in the primary endpoint analysis. PLMS per hour decreased more with ropinirole (48.5 to 11.8), compared with placebo (35.7 to 34.2; adjusted treatment difference: -27.2; 95% confidence interval [CI]: -39.1, -15.4; P < .0001). Periodic limb movements with arousal per hour decreased from 7.0 to 2.5 with ropinirole but increased from 4.2 to 6.0 with placebo (adjusted treatment difference: -4.3, 95% CI: -7.6, -1.1; P = .0096). Periodic limb movements while awake per hour decreased from 56.5 to 23.6 with ropinirole but increased from 46.6 to 56.1 with placebo (adjusted treatment difference: -39.5; 95% CI: -56.9, -22.1; P < .0001). Ropinirole treatment significantly improved patients' ability to initiate sleep (P < .05) and the amount of Stage 2 sleep compared with placebo (P < .001). There were also non-significant trends toward increases in total sleep time and sleep efficiency. Sleep adequacy (measured on the subjective Medical Outcomes Study sleep scale) was significantly improved with ropinirole treatment (adjusted treatment difference: 12.1; 95% CI: 1.1, 23.1; P = .0316). In contrast, the placebo group showed a greater increase in Stage 3/4 sleep (P < .01). No serious adverse events occurred in either group. CONCLUSIONS: Ropinirole is effective in the treatment of both the sleep and waking symptoms of RLS.

Antiparkinson Agents↗