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[Restless legs. A much neglected syndrome].

Ekbom's syndrome, or 'restless legs syndrome' (RLS), not only causes symptoms in the extremities during waking hours, but also sleep disturbance and daytime fatigue. Although the prevalence of RLS has been estimated to be 1-5%, the condition is probably underdiagnosed and undertreated. Its onset may occur at any age, and there may be long periods of remission, but the condition is generally chronic. In its primary form, there is often a family history of the disorder suggestive of an autosomal dominant mode of inheritance, where the results of EMG (electromyography) and nerve conduction studies are normal. In secondary forms, clinical signs and laboratory evidence of an associated abnormality are present. The most characteristic symptom of RLS is the spontaneous occurrence of paraesthesia or dysaesthesia during waking hours. The symptoms of RLS are worse or exclusively present during rest, and are partially or temporarily relieved by activity. About 80 per cent of RLS patients also suffer from 'periodic limb movements during sleep' (PLMS), which may cause microarousals during sleep. The diagnosis of RLS is based on characteristic clinical criteria, and the sleep disturbance is diagnosed polysomnographically. L-dopa and clonazepam have been found successful in the treatment of primary RLS, though lifelong treatment is often necessary.

Adolescent↗

Myoclonus in familial restless legs syndrome.

Eighteen members of a family were affected over a span of five generations with the restless legs syndrome, transmitted as an autosomal dominant trait. Ten patients had myoclonus. The propositus, a 57-year-old man, suffered from repeated, intense, asymmetric flexion jerks of the lower extremities, alternating with fidgeting and friction movements of the legs; all occurred at night prior to sleep and severely interfering with it. The patient's movements ceased with the onset of stage 1 sleep, while in his brother, the motor activity persisted in stages 1 and 2 of sleep.

Humans↗

[Pathophysiology of restless leg syndrome and periodic leg movement disorder in view of the latest research findings].

Both restless leg syndrome and periodic leg movement disorder have been classified as primary sleep disorders by the International Classification of Sleep Disorders. Considering the characteristic clinical symptoms, it is supposed that their pathomechanism involves the peripheral and central stimulus-processing mechanisms of the nervous system as well as several elements of the motor system. During the last couple of years many new elements of the pathomechanism have been discovered, in particular the dysfunction of the postsynaptic dopamine receptors related to the iron metabolism of the central nervous system, the role of opiate receptors, and the involvement of subclinical small fiber neuropathy. Many of these findings have been incorporated into the diagnostic and treatment protocols used in the management of patients with restless leg syndrome or periodic leg movement disorder. Considering the rapidly increasing number of publications on their pathomechanism and the various fields it involves, the authors found it necessary to evaluate these data and to interpret their relationships within the frame of sleep-wake regulation.

Central Nervous System↗

Human sleep and adrenal individual reactions to exercise.

Six fit men, aged 20, participated in the 16 day experiment. After a 5 day control period, the subjects marched on 6 consecutive days (from 09:00 h to 17:00 h) for 34 km/day at a speed of 6 km/h, with a backpack adjusted to complete a 35% of individual VO2 max energy expenditure. Control conditions were resumed for a 5 day recovery period. Sleep records were taken every night from 22:00 h to 06:00 h. Urinary 17-hydroxycorticosteroids (17-OHCS) were analysed from a 09:00 h to 17:00 h sample and from overnight urines. Two groups of subjects were defined by their responses to exercise. Four subjects exhibited an increase in stage 3 during the last third of the exercise nights (mean: 163.8 +/- 7.3% of control values) without any change in their adrenal response. Two subjects had no change or a slight decrease in stage 3 but showed increased 09:00--17:00 h 17-OHCS urine excretion (mean: 147 +/- 13% of control values). Sleep latencies were decreased in both groups. However, the 2 subjects of the second group exhibited increased restlessness as measured by the levels of wakefulness, stage 1 and EMG activity. In all subjects, paradoxical sleep was not altered, along with an unchanged all-night excretion of 17-OHCS. It is suggested that differences in adrenal responses to exercise may be responsible for differences in sleep quality. This could explain the discrepancies encountered in the literature about sleep variations after physical exercise.

17-Hydroxycorticosteroids↗

[Therapy of idiopathic and uremic restless legs syndrome].

Sensory and motor symptoms of the limbs, motor restlessness and an urge to move only at rest are the characteristics of the restless legs syndrome (RLS), which often leads to severe sleep disturbances. The clinical diagnosis can be made on the basis of the typical history, normal neurological findings and, in some cases, a positive family history, and can be confirmed by polysomnography. The indication for treatment depends on the patient's discomfort and the severity of the sleep disturbances. L-DOPA is the treatment of first choice both in idiopathic and uremic RLS. A bedtime dose of 100-200 mg L-DOPA standard plus decarboxylase inhibitor is effective against mild and moderate sleep disturbances in RLS. Titration of the dosage and additional treatment with sustained-release preparations of L-DOPA should be applied individually. Opioids and dopamine agonists are effective alternative treatments in idiopathic RLS. Benzodiazepines are indicated only in individual cases. Besides L-DOPA, uremic RLS patients can be treated with opioids and benzodiazepines. Various approaches in the treatment of idiopathic and uremic RLS are reviewed and the practical management of therapy is outlined.

Central Nervous System Agents↗

Sleep disorders.

Many pharmacologic and nonpharmacologic strategies are available to treat sleep disorders successfully. Conventional stimulants and the new stimulant modafinil have roles to play in the management of narcolepsy and idiopathic hypersomnia. Knowledge of the properties and clinical effects of these drugs allows adequate doses of medications to be used with the goal of attaining as maximal alertness as possible. A range of dopaminergic agents is available to treat restless legs syndrome; other medications such as opiates, benzodiazepines, and anticonvulsants can also be used. Successful use of the dopaminergic agents depends on an understanding of the phenomena of augmentation, rebound, and tolerance. Arousal parasomnias can be treated with behavioral methods such as hypnosis and drug therapy. Clonazepam provides relief of the symptoms in most patients with REM sleep behavior disorder.

Disorders of Excessive Somnolence↗

Restless legs syndrome associated with primary hyperparathyroidism.

Restless legs syndrome (RLS) is a poorly understood sleep-related movement disorder which can be primary or associated with other conditions, most commonly iron deficiency, uremia and peripheral nerve disease. We present a case of RLS with an unusual secondary cause: primary hyperparathyroidism with hypercalcemia. This patient experienced complete and sustained relief of RLS symptoms immediately after parathyroidectomy, with normalization of her serum parathyroid hormone (PTH) and calcium levels. Early recognition and treatment of this uncommonly detected underlying cause is important because it is potentially curative in this frequently disabling condition for which usually only symptomatic treatment is available.

Female↗

[Topiramate use as treatment in restless legs syndrome].

INTRODUCTION: Restless legs syndrome is an underdiagnosed disorder of unknown etiology, that generates severe sleep and life quality disturbances. In its therapeutic approach, drugs with very different action mechanisms and variable results have been used. METHODS: Nineteen outpatients diagnosed of restless legs syndrome were studied observationally. A semistructured interview was carried out and physical variables (weight, arterial pressure and heart rate), sensitive and motor symptoms, effective dose of topiramate, side effects and fulfillment of the treatment at 30, 60 and 90 days were studied. RESULTS: The patients studied, with an average age of 62.052 +/- 6.22 years, showed improvement in sensitive and motor symptoms, as well as non-significant reductions in cardiovascular parameters. The mean effective dose of topiramate was established at 42.1 +/- 18.7 mg. A significant reduction in weight stands out among the side effects. CONCLUSIONS: Topiramate is profiled as an effective treatment in restless legs syndrome, with good tolerability and minimal side effects.

Aged↗

Sleep in detoxified alcoholics: impairment of most standard sleep parameters and increased risk for sleep apnea, but not for myoclonias--a controlled study.

OBJECTIVE: To assess recently alcohol-abstinent chronic alcoholic patients for selected parameters indicative of sleep quality. METHOD: Patients (n = 24, 14 male), abstinent 3-6 weeks, and healthy controls (n = 20) were admitted to a clinical sleep unit. Measurements included sleep respiratory events and periodic limb movements, using strict methodology. RESULTS: Clear signs of sleep deterioration and a high prevalence of apneic/hypopneic episodes were observed. Apneas were found at the same frequency for men and women; this has not been described before. No periodic limb movement was found. CONCLUSIONS: Considering the high degree of morbidity and mortality observed in sleep apneic syndrome, systematic screening for sleep apneas is recommended for alcoholics seeking help.

Adult↗

The primary restless legs syndrome pathogenesis depends on the dysfunction of EEG alpha activity.

A dopaminergic drug - lisuride exhibited increase in alpha, decrease in beta and slow activities on brain function measured by computerized EEG. It was postulated that reverse EEG changes might play role in the pathogenesis of RLS. During transition from wakefulness to sleep stage 1 changes in alpha activity initiate long-lasting alpha arousal responses and they continue increasingly at sleep stage 2. This dysfunction is probably due to a genetic vulnerability of EEG alpha rhythm and disinhibits the diencephalospinal dopamine system, mostly during sleep but also during wakefulness. The disinhibition produces background for activation of PLMs, disturbing sensations in brainstem and urge to move, motor restlessness at cerebral cortex, generally for legs. All lead to severe insomnia. In RLS patients, forced deviations from alpha to theta or beta activity are unsuitable and resting EEGs reflect a dopamine receptor-specific 'individual sensitivity.' This vulnerability is alleviated after lisuride with suitable CEEG changes.

Brain↗

Long-term course of restless legs syndrome in dialysis patients after kidney transplantation.

Restless legs syndrome (RLS) is a common cause of sleep disturbance and is frequently experienced by hemodialysis patients. Factors triggering the disease in uremia have not yet been identified. To our knowledge, the course of RLS symptoms after kidney transplantation has not been investigated systematically. We investigated the clinical long-term course of RLS in hemodialysis patients who underwent kidney transplantation. Patients were given a standardized questionnaire three times: at baseline, and twice after their kidney transplants. The severity of RLS was rated by the patients (0 =no symptoms, 10 = very severe symptoms). The description of the final outcome was based on the last follow-up visit. Eleven of 64 hemodialysis patients with RLS received a transplant (5 men, 6 women; severity of RLS at baseline, 7.8 +/- 0.7 [mean +/- SEM]). In all patients, RLS symptoms disappeared within 1 to 21 days after transplantation. At follow-up visits, 4 patients whose transplanted kidneys still functioned well were still free of RLS symptoms up to the longest follow-up period of 9 years. In 3 other patients, RLS symptoms gradually reappeared (severity, 1 +/- 0). In 3 of 11 patients, the transplant failed and RLS symptoms reoccurred within 10 days to 2 months (severity, 7.3 +/- 2.6). RLS symptoms reoccurred in 1 patient with failure of the transplant but disappeared again after a second, successful transplant. Kidney transplantation has a strong and positive influence on RLS symptoms in hemodialysis patients. Hemodialysis patients can expect a substantial improvement of RLS symptoms after a successful kidney transplant.

Adult↗

Sleep disturbance in cancer patients.

Sleep difficulty is a prominent concern of cancer patients, yet there has been no large study of the prevalence and nature of sleep disturbance in cancer patients. This cross-sectional survey study examined: (a) the prevalence of reported sleep problems in patients attending six clinics at a regional cancer centre; (b) sleep problem prevalence in relation to cancer treatment; and (c) the nature of reported insomnia (type, duration, and associated factors). For three months, all patients attending clinics for breast, gastrointestinal, genitourinary, gynecologic, lung, and non-melanoma skin cancers were offered a brief sleep questionnaire. Response rate was 87%; the final sample size was 982. Mean age of respondents was 64.9 years (SD 12.5). The most prevalent problems were excessive fatigue (44% of patients), leg restlessness (41%). insomnia (31%), and excessive sleepiness (28%). Chi square tests showed significant variation among clinics in the prevalence of most sleep problems. The lung clinic had the highest or second-highest prevalence of problems. The breast clinic had a high prevalence of insomnia and fatigue. Recent cancer treatment was associated with excessive fatigue and hypersomnolence. Insomnia commonly involved multiple awakenings (76% of cases) and duration > or = 6 months (75% of cases). In 48% of cases, insomnia onset was reported to occur around the time of cancer diagnosis (falling within the period 6 months pre-diagnosis to 18 months post-diagnosis). The most frequently identified contributors to insomnia were thoughts, concerns, and pain/discomfort. In a multivariate logistic regression analysis, variables associated with increased odds of insomnia were fatigue, age (inverse relationship), leg restlessness, sedative/hypnotic use, low or variable mood, dreams, concerns, and recent cancer surgery. This study provides new information about sleep-related phenomena in cancer patients, information which will be useful in planning supportive care services for cancer patients.

Adult↗

Sleep apnea and sleep-related periodic leg movements in community resident seniors.

The elderly have a high incidence of sleep complaints. A high incidence of sleep apnea (SA) and sleep-related periodic leg movements (PLMs) is also suspected. The relationship between the incidence and severity of SA and PLMs and sleep complaints has not, however, been determined in terms of symptomatology and physiologic abnormality. In a group of 46 community resident seniors (60 to 95 years old), the incidence of SA and PLMs was correlated with subjective sleep-wake complaints. Sixty-one percent of subjects had SA and/or PLMs. Apneas/hypopneas were associated with an average oxygen desaturation of less than 5% and an average change in heart rate of less than 10 beats per minute. While subjects with SA or PLMs had clear evidence of objective sleep disturbance, only one quarter of them admitted to any subjective sleep complaints or daytime sleepiness. Furthermore, severity of SA or PLMs failed to predict sleep-wake complaints, and vice versa. This study confirms that typically mild SA and PLMs are widespread in the elderly but tend not to be manifested in sleep-wake complaints and probably go untreated as a result. Further research is needed to determine any long-term medical significance.

Aged↗

Severe, childhood-onset, idiopathic, life-long insomnia responding selectively to opiate therapy: case report with 19 year follow-up.

BACKGROUND: Idiopathic (primary) insomnia can be difficult to treat; only two prior cases responsive to opiate therapy have been reported. A case is now presented of severe, idiopathic, childhood-onset, familial insomnia, with increased libido, absence of psychopathology, tardive emergence of restless legs syndrome (RLS), and selective response to opiate therapy. CASE REPORT: A 39-year-old woman was referred in 1981 by her physician who had discovered 3 years earlier that propoxyphene treatment of migraines also controlled her chronic insomnia. She had experienced severe insomnia since childhood, and during early adulthood the insomnia intensified, as she would sleep 0-3 h nightly and never napped. Daily generalized motor restlessness resulted in her frequently walking around the house while feeling exhausted. The quality of her life was considerably compromised by her insomnia, motor restlessness, and by an increased libido that was present since puberty and that was only partially relieved by having sex repeatedly with her husband. RESULTS: Nightly opiate therapy for 19 years has controlled the insomnia, motor restlessness, and excessive libido without affecting her normal libido. The insomnia had not responded to treatment with >25 agents covering >10 pharmacologic categories. During her first (unmedicated) polysomnographic (PSG) study in 1981, she slept 0 min while spending 436 min in bed. In 1984, four consecutive PSG studies were conducted in a design that confirmed the efficacy of propoxyphene therapy of her insomnia. In 1990, an ambulatory PSG revealed two runs of EEG rhythmic paroxysmal activity arising from sleep and wakefulness, without clinical correlate. Neurologic history was negative for seizures, but positive for complete right carotid artery occlusion and three transient ischemic attacks. At age 55 years, typical RLS emerged that was controlled with levodopa therapy, and a concurrent relapse of insomnia was controlled with oxycodone replacing propoxyphene. CONCLUSIONS: Nightly opiate therapy of severe idiopathic (primary) insomnia can remain effective during very long-term clinical follow-up. Guidelines are provided for when to consider such an unusual treatment in other cases of severe, chronic insomnia.

Journal Article↗

Emergent psychopathology in Alzheimer's disease patients over 12 months associated with functional, not cognitive, changes.

In a large, well-characterized population of community-dwelling persons with Alzheimer's disease (AD), we investigated the emergence of behavioral symptomatology and its association with changes in cognitive, global-clinical, and functional status. Behavioral Rating Scale for Dementia (BRSD) item responses from 235 AD patients with varying levels of dementia severity and without significant behavioral disturbance were taken from the baseline and 12-month visits in a study of cognitive and behavioral instruments. Item-level analysis revealed new symptoms at every dementia severity level. The symptoms that emerged in the greatest proportion of patients were change in weight, change in appetite, diurnal confusion, uncooperativeness, restlessness, clingy behavior, loss of initiative, and change in sleeping pattern. Changes in cognitive status over the 12 months were associated with changes in functional status and not with the emergence of behavioral symptomatology; however, change in the latter two domains tended to be associated. The findings support the hypothesis that increasing behavioral disturbance is not strongly associated with decreasing cognitive status and that, except for psychotic symptoms, a previously observed association between dementia severity and behavioral status may have been mediated partly by changes in functional abilities.

Activities of Daily Living↗

Polysomnographic and MMPI characteristics of patients with insomnia.

This report represents the polysomnographic aspects of sleep and the psychological characteristics of a large series of patients with insomnia classified according to the diagnostic system of the Association of Sleep Disorders Centers. The findings for patients in the various diagnostic categories were compared to those of symptomatic patients with no objective findings. 9 specific diagnoses were made, but 4 diagnoses accounted for the majority of patients. The 4 most prevalent were psychophysiological disorders (15%), psychiatric disorders (17%), nocturnal myoclonus and restless legs (18%), and no objective findings (19%). Patients of a sleep disorders center are a select population and may not be representative of the general population of patients with insomnia complaints. The psychological characteristics of the different diagnostic groups were assessed by computing the number of elevations on the MMPI. Patients with a psychiatric diagnosis exhibited the highest number of MMPI elevations, as might be expected. Patients with nocturnal myoclonus had the lowest number of elevations. The other groups did not significantly differ from the group with no objective findings. Polysomnographic measures of sleep differed considerably among the diagnostic groups. The groups with medical disorders, respiratory impairment, atypical polysomnographic features, and nocturnal myoclonus had similar short sleep latencies to those of the group with no objective findings. With longer wake times before sleep and significantly different from patients with no objective findings were the psychophysiological disorder, psychiatric disorder and drug and alcohol groups. Patients with a circadian rhythm disturbance had the longest latencies.(ABSTRACT TRUNCATED AT 250 WORDS)

Circadian Rhythm↗

Factors that disturb sleep in nursing home residents.

The purpose of this cross-sectional survey was to examine subjective sleep quality, and identify factors that disturb sleep in cognitively intact nursing home (NH) residents. We interviewed 51 cognitively intact NH residents using a validated instrument, the Pittsburgh Sleep Quality Index (PSQI). Questions regarding the environment, symptoms suggestive of restless leg syndrome, and periodic leg movements were also asked. Three individuals were unable to answer all the questions and, therefore, analyses were performed on 48 subjects. Seventy-three percent of the subjects were identified as "poor" sleepers based upon a total PSQI score > 5. Factors that disturbed the residents' sleep three or more times a week were: nocturia (71%), environment-related noise or light (38%), pain (33%), feeling too hot (6%) and leg cramps (6%). On multiple regression analysis, poor sleep correlated with depressive symptoms and comorbidity, not with age or gender. Poor sleep quality is common among cognitively intact NH residents. In our study, nocturia, environmental factors and pain were the most commonly perceived causes of sleep disturbance. Poor sleep independently correlated with depressive symptoms and comorbidity. These findings should be kept in mind when evaluating sleep complaints in the nursing home.

Aged↗

Improving symptoms of senile dementia by a night-time spa bathing.

In our medical and welfare facilities, many patients with senile dementia require aid in taking a bath. In most institutions, patients usually take a bath in the daytime within the working hours of the staff. However, most of these patients used to take a bath in the evening or at night at their homes. Some patients even fall asleep after daylight bathing. Thus, we studied the stabilizing effects of night-time spa bathing on symptoms associated with dementia. Ten patients (two male and eight females, aged 75-88) in special nursing institution for the aged, were enrolled in this study. They were all assessed as +4 on the Karasawa's clinical criteria for grading dementia. For 9 weeks, night-time spa bathing was performed at 18:00-19:00 twice a week. Except for the night-time spa bathing period, the bathing hour was 14:00-15:00 as usual. The observations of symptoms including restlessness, wandering and aggression were carried out ten times daily along with those on sleeping condition five times daily, to compare symptoms and conditions during 2 weeks of baseline daytime bathing periods, 9 weeks of night-time bathing periods and 2 weeks of daytime bathing periods, totaling 13 weeks. The results showed that sleeping conditions were ameliorated in more than 60-90% of the subjects. Their sleeping conditions began to improve 2 weeks after the start of night-time spa bathing with a remarkably improvement 4-6 weeks after the start. Restlessness was recognized in six subjects, wandering in eight and aggression in four at baseline, and 75-100% of the subjects with such symptoms improved markedly.

Journal Article↗