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PubMed2004

Treatment of nocturnal disturbances and excessive daytime sleepiness in Parkinson's disease.

Nocturnal disturbances are common in Parkinson's disease (PD) patients, with almost 70% of these patients reporting nocturnal disturbances. The etiology of sleep disturbances in patients with PD is still controversial. They might be dependent on dopaminergic drugs, on disease progression, or on a combination of these two factors. Nocturnal disturbances can be categorized in four groups: 1) PD-related motor symptoms, including nocturnal akinesia, early-morning dystonia, painful cramps, tremor, and difficulty turning in bed; 2) treatment-related nocturnal disturbances; 3) psychiatric symptoms, including hallucinations, vivid dreams, depression, dementia, insomnia, psychosis, and panic attacks; 4) other sleep disorders, including insomnia, REM behavioral disorder (RBD), restless legs syndrome (RLS), periodic leg movements (PLMS), and excessive daytime sleepiness (EDS). Specific treatment options are supplied for every group. A global evaluation of nocturnal disturbances would provide clinicians with a valuable tool to establish an optimal regimen that could positively influence all nocturnal disturbance categories and thus improve PD management on. However, it is important to consider that management of some nocturnal disturbances in a group may worsen nocturnal symptoms of another group or may increase EDS. PD-related symptoms can be treated with long-acting DA agonists to obtain continuous DA receptor stimulation during the night. Both treatment-related nocturnal disturbances and psychiatric symptoms may be related to drug treatment, and therefore, in both cases, drug reduction or discontinuance should be considered. Some sleep disorders, such as RLS and PLMS, may be controlled by DA agents, and others, such as insomnia and EDS, may be improved by reducing dopaminergic stimulation.

Antiparkinson Agents↗

PubMed2004

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.

Adolescent↗

PubMed2006

Clinical characteristics of Restless legs syndrome in patients with Parkinson's disease.

To assess the characteristics, clinical significance and pathology of Restless legs syndrome (RLS) in patients with Parkinson's disease (PD), we studied clinical backgrounds, RLS symptoms, polysomnographic (PSG) variables and therapeutic outcomes in 13 PD patients with RLS (pRLS), and compared them with those of 22 idiopathic RLS patients (iRLS). In all but one pRLS patient, RLS symptoms arose within 5 years of PD onset. pRLS patients had a lower prevalence of family history of RLS, and the age at onset was higher than in iRLS subjects. Scores for the severity scale established by the International Restless Legs Syndrome Study Group (IRLS), the Pittsburgh Sleep Quality Index, and the suggested immobilization test did not differ between groups. However, the periodic limb movements index measured by polysomnogram was smaller in pRLS subjects. After RLS treatment, symptoms improved significantly in both groups; however, pRLS subjects showed higher IRLS scores despite receiving similar doses of RLS medications. The severity of RLS before treatment was quite similar between the two groups, but the response to treatment could be poorer in pRLS than in iRLS. Thus, degeneration of the diencephalospinal dopaminergic pathway due to PD itself and physiological aging could overlap in the pathology of pRLS.

Age of Onset↗

PubMed2005

Variability of periodic leg movements in various sleep disorders: implications for clinical and pathophysiologic studies.

STUDY OBJECTIVES: Periodic leg movements in sleep (PLMS) are a frequent phenomenon in various sleep disorders. The pathophysiology of PLMS is still not understood, but recent studies indicate a hypoactivity of the dopaminergic system in subjects with PLMS. In the present study, we investigated the intrasubject variance of PLMS from one night to the other because a fluctuation in the number of PLMS may influence the outcome of pharmacologic and pathophysiologic studies. DESIGN: Retrospective observational study. SETTING: Data collection occurred in the sleep disorders unit. PATIENTS: Sleep electroencephalogram and PLMS data of 115 patients with PLMS monitoring over 2 consecutive nights were evaluated retrospectively. Patients were grouped into the following diagnostic categories: restless legs syndrome, insomnia secondary to a psychiatric disorder, primary insomnia, sleep apnea syndrome, and narcolepsy or idiopathic hypersomnia. INTERVENTIONS: N/A. RESULTS: In 27% of the entire patient population, we found a considerable variability of the PLMS index (difference between nights > 10/hour) and, in 19% of patients, variability of the PLMS arousal index (difference between nights > 5/hour) across the 2 investigated nights. The intraindividual variance occurred most frequently and to the highest extent in patients with RLS. CONCLUSIONS: The variability of PLMS indexes should considered if the PLMS recording is performed in support of the clinical diagnosis or in the interpretation of studies investigating drug efficacy. Furthermore, the variability of PLMS may be an indicator of an instability of the dopaminergic system that should be taken into account in studies investigating central nervous system dopaminergic activity.

Circadian Rhythm↗

PubMed1996

Periodic limb movements and restless legs syndrome.

The criteria that characterize restless legs syndrome (RLS) and the differential diagnoses are discussed. Clinical signs include sleep disturbance, involuntary movements in sleep or wakefulness, a normal neurologic examination, a chronic clinical course, and, in some cases, a positive family history. Periodic limb movements during sleep, which also may occur as an isolated finding, may or may not cause frequent arousals or awakenings. Clinical diagnosis of idiopathic or symptomatic forms of RLS can be supported with polysomnography. Treatment of first choice consists of dopaminergic drugs or dopamine agonist followed by opioids or benzodiazepines.

Adult↗

PubMed1996

Sleep complaints in postpolio syndrome.

OBJECTIVE: This study evaluated the prevalence of sleep-related and sleep-disordered-breathing (SDB)-related complaints in a group of postpolio patients compared with healthy controls. DESIGN: A questionnaire, consisting of the validated Sleep Wake Experience List (SWEL), and a list of questions pertaining to sleep-disordered breathing (SDB), was mailed to a group of 43 postpolio patients. PARTICIPANTS: The patient group consisted of 43 former polio patients who had been evaluated at a neuromuscular disease clinic in a tertiary referral center for new complaints of progressive muscle weakness. The patients were requested to select two healthy controls from their neighborhood who also filled out a questionnaire. RESULTS: In the group of postpolio patients the frequency of tiredness on waking up and during the day, headache on waking up, daytime sleepiness, and restless legs was significantly higher compared with the control group. Complaints specifically related to SDB, such as apneas and snoring, were not mentioned significantly more often by the postpolio patients. CONCLUSION: Up to half of postpolio patients report complaints of disordered sleep, which is likely to influence daytime functioning. Further studies, including sleep studies into SDB and restless legs, are necessary to elucidate the causes for these complaints.

Female↗

PubMed1979

Effects of maternal drinking on neonate state regulation.

Sleep-awake state distribution during inter-feed intervals over a 24-hour period on the third day of life was investigated by means of a continuous non-intrusive bassinet sleep monitor. 31 infants were studied: 14 born to mothers who drank heavily throughout pregnancy (group A), eight whose mothers modified their heavy drinking (group B) and nine whose mothers never were heavy drinkers (group C). Over the 24-hour period, group A infants slept less than those in group B. In comparison with group C, group A infants had a larger proportion of quiet sleep episodes interrupted by awake or unclassified epochs, and were more restless, with more frequent major body movements. These pilot observations suggest that heavy maternal consumption of alcohol, when continued throughout pregnancy, is associated with a disturbance of sleep-awake state distribution. Successful therapy of heavy drinking during pregnancy may improve the physiological competence of the newborn to regulate sleep-awake states and facilitate interaction between mother and infant.

Adolescent↗

PubMed2002

Motor pattern of periodic limb movements in sleep in idiopathic RLS patients.

OBJECTIVE: Periodic limb movements in sleep (PLMS) are recurrent sleep-related movements that often occur in association with restless legs syndrome (RLS). The purpose of the present study was to examine the pathophysiology of PLMS in patients with idiopathic RLS. METHODS: Ten patients with idiopathic RLS who were medication-free or who had withdrawn from medication at least 2 weeks prior to the study underwent an extensive neurophysiological investigation that included nocturnal video-polysomnographic recording (VPSG), EMG recording, and the Multiple Sleep Latency Test (MSLT). Sleep efficiency and PLMS index were calculated during VPSG. RESULTS: All patients had an increased PLMS index, decreased sleep efficiency, and a pathological MSLT score. Leg muscles were the first to be activated, often with alternation of side, and no constant recruitment pattern could be found from one episode of PLMS to another, even in the same patient. No ordinate caudal or rostral spread of the EMG activity was observed. CONCLUSIONS: The results suggest that there are different, independent, and unsynchronized generators for PLMS. The direct participation of the cerebral cortex in the origin of PLMS is unlikely, suggesting that abnormal spinal cord hyperexcitability may act as the primary cause of PLMS, triggered by unidentified sleep-related factors.

Journal Article↗

PubMed2006

Epidemiology of familial and sporadic restless legs syndrome in Iran.

Restless legs syndrome is one of the most common sleep and movement disorders. For lack of sufficient information on this syndrome in Iran, this study was conducted at Alzahra Hospital, Isfahan, Central Iran, to determine the epidemiology of idiopathic, familial and sporadic forms of the syndrome. From September 1999 to April 2003, 61 patients in two groups were selected. A questionnaire with emphasis on sleep history and neurological history was completed and a thorough physical examination was performed for each patient. Familial and sporadic groups had mean +/- SD ages of 22 +/- 2.1 and 41 +/- 3.2 years, respectively (P < 0.05). Female to male ratio was 2:1. The mean +/- SD ages for women and men were 31 +/- 5.3 and 42 +/- 6.1 years (P < 0.05), respectively. Our findings support the current opinion that restless legs syndrome should be divided into the early-onset disease with a clear genetic component and the late-onset disease with an unclear etiology.

Adult↗

PubMed1995

New actigraphic assessment method for periodic leg movements (PLM).

A new actigraphic method by which periodic leg movements (PLM) can be measured is presented. Data acquistion and analysis were brought into line to distinguish short-lasting repetive leg movements from random motor restlessness. The definition of PLM follows the generally accepted criteria for PLM scoring. Thirty restless legs patients, all also suffering from PLM, were investigated three times by polysomnography, including tibialis anterior surface electromyography and actigraphy. A high correlation (reliability) was found for the number of PLM per hour spent in bed between the two methods. Furthermore, the actigraph records PLM specifically. An index of random motor restlessness is not sufficient for a reliable PLM according. In addition, periodic movements in sleep (PMS) and PLM show comparable variability in general. The actigraphic assessment of PLM, however, gives a better measure because PMS recordings may result in a substantial underestimation of PLM when sleep efficiency is reduced. This method is an ambulatory assessment tool that can also be used for screening purposes.

Adult↗

PubMed1996

Restless legs syndrome in end-stage renal disease.

The aim of this study was to evaluate the prevalence of restless legs syndrome (RLS) in patients with end-stage renal disease (ESRD), and to determine its association with sleep disorders and premature discontinuation of dialysis ("sign-offs"). End-stage renal disease patients (N = 204) and a control group of patients with heart disease (N = 129) completed a self-administered questionnaire regarding symptoms of RLS, sleep habits, pruritus, and adherence to dialysis therapy. Laboratory measures and sensory nerve amplitudes were collected on the ESRD patients. Twenty percent of the ESRD patients and 6% of the cardiac patients reported moderate to severe RLS symptomatology. Sleep onset was delayed and total sleep time was diminished in ESRD patients compared with cardiac patients. Symptoms of RLS were directly correlated with all sleep measures as well as with pruritus. Symptoms of RLS, sleep onset latency, and transferrin saturation were independently associated with premature discontinuation of dialysis. Significantly increased risk for mortality was observed in patients with RLS at the 2.5-year follow-up. Restless legs syndrome is a common finding in patients with ESRD and is associated with substantial morbidity.

Female↗

PubMed1999

The influence of sex, age and sleep/wake state on characteristics of periodic leg movements in restless legs syndrome patients.

Restless legs syndrome (RLS) patients experience periodic stereotyped leg movements while awake and during sleep. The aim of the present study was to measure the effects of sex, age and the sleep/wake state on several characteristics (frequency, duration and periodicity) of these periodic leg movements (PLM). One hundred unrelated patients diagnosed with primary RLS were studied. During wakefulness, frequency of PLM increased and the mean inter-movement interval decreased with advancing age. The modal value of inter-movement interval distribution was also altered suggesting that aging influences rhythm-generation mechanisms. Sleep/wake states had a profound effect on leg movement characteristics. Movements of longer duration were seen during wakefulness, while REM sleep was characterized by the shorter duration and the lowest frequency of PLM, due most likely to the inhibition of spinal motoneurons that prevails in REM sleep. States of vigilance also modulated the periodicity of PLM. Intervals were shorter during wakefulness and increased progressively from stage 1 to stage 2 sleep, and to slow wave sleep (SWS). During REM, the duration of sleep intervals returned to values obtained in stage 1 sleep; these two stages sharing similar patterns of EEG activity. These results indicate that a single state dependent mechanism may be responsible for the periodicity of PLM noted both during sleep and wakefulness.

Adult↗

PubMed2002

Restless legs syndrome: a sensorimotor disorder of sleep/wake motor regulation.

Restless legs syndrome (RLS) remains an underappreciated sensorimotor disorder of sleep/wake regulation. It is one of the few sensorimotor disorders that is provoked by rest and that also follows a clear circadian pattern. Recent epidemiologic studies have verified that the condition is common in populations derived from the north and west of Europe, and have begun to uncover some of the genetic substrate of the disorder. New instruments have been developed to facilitate diagnosis and assessment of severity. The pathogenesis of the condition remains uncertain, but recent discoveries implicate areas of the nervous system from the spinal cord up to the basal ganglia. A current hypothesis undergoing vigorous exploration is that the condition results from a deficiency of dopaminergic function based on abnormalities of iron transport and storage. Therapeutically, studies have shown the dopamine agonists to be the most reliable treatment for severe cases, whereas other recent studies have successfully utilized a number of other medications, including levodopa, opioids, and anticonvulsants. New standards provide guidelines for management of RLS and make specific pharmacotherapeutic recommendations.

Humans↗

PubMed1986

Pharmacotherapy in Alzheimer's disease: basis and rationale.

Alzheimer's disease is a slowly progressive disorder involving deterioration of both intellect and personality. The neuropathological features of Alzheimer's disease include abundant neurocortical senile plaques and neurofibrillary tangles. Drug therapies of Alzheimer's disease have been based on empirical observations of the signs and symptoms of the disease and have included the use of hypnotics to reverse insomnia or inverse sleep rhythms; anxiolytics to relieve anxiety, tension and restlessness antipsychotics to "tranquilize" or control psychotic symptoms, such as delusions and hallucinations; stimulants to overcome withdrawn behavior or lethargy; and lastly, antidepressants to control depression. Our growing knowledge of neuropathological and neurochemical changes associated with normal aging and Alzheimer's disease has made it possible to explore and develop pharmacologically-based therapies in Alzheimer's disease. Recent research has revealed behavioral symptoms associated with underlying biochemical changes in either the cholinergic, dopaminergic/ GABAergic (gama-aminobutyric acid) noradrenergic, serotoninergic, neurochemical and/or neuropeptidergic systems. Pharmacological strategies involving manipulation of these systems as a means of relieving Alzheimer's disease symptoms will be reviewed from several perspectives, e.g., those involving transmitter substitution, enzyme inhibition and direct specific receptor stimulation.

Alzheimer Disease↗

PubMed2005

Oxygen as a therapy for reducing nicotine withdrawal symptoms.

Nicotine addiction leads to withdrawal symptoms in many persons who quit smoking. In addition to craving, the most commonly experienced symptoms are: depression; difficulty sleeping; irritability, frustration, or anger; anxiety; difficulty concentrating; restlessness; decreased heart rate; and increased appetite or weight gain. The severity of withdrawal symptoms are variable, and often lead to relapse. By altering the course of withdrawal symptoms it is possible to improve the chances of the quit attempt and reduce the risk of relapse. There is strong evidence that dopamine is the primary neurotransmitter in the reward pathway in addiction. The use of nicotine replacement therapies and Zyban (sustained release bupropion hydrochloride), both of which are suspected of exploiting dopamine's role in addiction, enhance the likelihood of long-term smoking cessation. Anecdotal reports of oxygen's capacity to reduce both the desire for nicotine and withdrawal symptoms suggest that this may be a therapeutic possibility for those who do not experience success with more traditional cessation approaches. Oxygen may have a favorable effect on nicotine withdrawal, as it appears to alter the balance of central neurotransmitters such as dopamine.

Brain↗

PubMed2001

Clearance of melatonin and 6-sulfatoxymelatonin by hemodialysis in patients with end-stage renal disease.

Patients with end-stage renal disease (ESRD) suffer from a number of related disorders. These include endocrine abnormalities, sleep disturbances, and depression. Melatonin is involved in the synchronization of exogenous zeitgebers with the endogenous rhythms, and it has effects on various psychological factors. As the concentrations of melatonin and the effects of dialysis have only occasionally been investigated in ESRD, we performed a study involving 35 patients, measuring the serum concentrations of melatonin, and of its major metabolite 6-sulfatoxymelatonin (aMT6s), before and after hemodialysis. Serum samples taken during morning hours from a control group (n=11) with intact kidneys served as controls. Patients were dialyzed for approximately 4 hr between 07:00 and 13:00 hr (S1), between 13:00 and 20:00 hr (S2), or between 18:30 and 22:30 hr (S3). Mean melatonin concentrations before hemodialysis were highly elevated when compared with the controls (40.6 vs. 6.7 pg/mL; P<0.001). Although melatonin levels were decreased to 20.3 pg/mL after dialysis, they were still well above the control levels. Likewise, aMT6s concentrations before dialysis were highly elevated in ESRD patients before dialysis when compared with controls (39.5 vs. 2.0 pg/mL; P<0.001), and also decreased by dialysis to levels still well above control levels (25.3 pg/mL). Clearance efficacy was better for melatonin (48.9%) than for aMT6s (36.6%; P<0.05). In ESRD patients, a diurnal rhythm for melatonin was observed (S1, 45.1 pg/mL; S2, 31.5 pg/mL; S3, 48.7 pg/mL; P<0.05), indicating that the normal synthesis rhythm is maintained. None of the following secondary disorders were correlated with melatonin concentrations: insomnia, delayed sleep onset, night-time arousals, and restless-leg syndrome. The reason for this observation is probably the melatonin concentrations, which were so high that no sub-classification could be identified. It is concluded that in ESRD patients, hemodialysis is unable to decrease elevated levels of melatonin and aMT6s to normal values. It is speculated that some of the secondary disorders in ESRD are caused by supraphysiological concentrations of melatonin.

Adult↗

PubMed1997

Correlation between K complex, periodic leg movements (PLM), and myoclonus during sleep in paraplegic adults before and after an acute physical activity.

K complex is the characteristic wave of stage II of sleep. The relationship between periodic limb movements (PLM) and the restless legs syndrome (RLS), and the incidence of K complexes and alpha activity has been previously described. The aim of the present study was to evaluate the effect of an acute physical activity upon K complex, PLM, and myoclonus during sleep in individuals who were paraplegic. We evaluated 84 polysomnograms from 28 volunteers with a spinal cord injury at the level of T7-T12, obtained during three consecutive nights. On day 3, the volunteers were submitted to a test of maximum effort (manual cycloergometer, with the equipment Cybex Met 300, with a progressive load increase of 12.5 w, every 2 min). The analysis of the polysomnographic recordings showed a positive correlation between the incidence of K complex and limb movements on nights 1, 2 and 3. Similarly, a correlation between the incidence of K complex and myoclonus was observed on nights 1, 2 and 3. An increased incidence of the total K complex was seen on night 3, 36 h after the test maximum effort. Both total K complex and K complex/h were reduced on night 2, compared to basal recording (night 1). There was a reduction of sleep latency on night 2, whereas total sleeping time increased progressively on night 3, as well as REM phase on nights 2 and 3. These findings indicate that physical activity can effect or modulate the incidence of K complex and suggest that a positive correlation between PLM and K complex may occur in those who are paraplegic from a spinal cord injury. In conclusion, sleep can be consolidated after physical activity.

Adult↗

PubMed1988

Exercise and psychologic well-being in the community.

In a representative sample of 401 adults in Illinois in 1984, the authors found that increased participation in exercise, sports, and physical activities is associated with improved psychologic well-being. Part of this association is through improved subjective physical health. The authors controlled for potentially confounding factors, including sociodemographic characteristics, instrumentalism, and overweight. They concluded that exercise is associated with decreased symptoms of depression (feelings that life is not worthwhile, low spirits, etc.), anxiety (restlessness, tension, etc.), and malaise (rundown feeling, trouble sleeping, etc.) in the general population, most of which is not severely depressed, and in which many persons are engaged in moderate, nonaerobic exercise.

Adolescent↗