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Query: UMLS:C0015672 (fatigue)
 51,768 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Fatigue is one of the most frequent and disabling symptoms in multiple sclerosis (MS) patients. This symptom's etiopathogenic mechanism, though not known, seems complex and multifactorial, and its therapeutic management is difficult. Different treatments have been tested in recent years, but a weak efficacy that may be limited in time has been observed. Recently, modafinil has been suggested as a possible treatment for fatigue in MS patients, although nowadays, the only use of modafinil approved by the Food and Drug Administration is narcolepsy. Modafinil, 2-([difenilmetil]sulfinil), acetamide is a state of wakeness promoter, and although its exact action mechanism is not known, it differs from other central nervous system stimulants because no dopaminergic activation is observed, and its action take place at the hypothalamic level. It is known that modafinil increases the proportion of high-frequency alpha waves and reduces delta and theta waves, increasing vigilance. Although few studies exist on modafinil in MS patients with fatigue, the results suggest this drug as a promising treatment, because of its efficacy and safety, and should encourage us to continue working in this area.
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PMID:[Modafinil and fatigue in multiple sclerosis]. 1547 May 83

Daytime tiredness or sleepiness and deficits in cognitive performance are common complaints in sleep disordered patients. Till now there are few studies comparing patients from different diagnostic groups of sleep disorders in the same experimental protocol. We studied the time course of cognitive functions and subjective alertness in a parallel group design with four groups of patients [narcolepsy, untreated or treated obstructive sleep apnea (OSA), or psychophysiological insomnia] and a control group of subjects without sleep complaints. Each group consisted of 10 subjects, matched for age and gender. After a night with polysomnography, subjects were studied for 10 h from 08:00 hours to 18:00 hours at 20 min intervals under standardized environmental conditions. Four psychological tests were applied, (1) a critical flicker fusion (CFF) test to measure optical fusion threshold (alertness); (2) a paper-and-pencil visual line tracking test (selective attention); (3) a visual analog scale (VAS) for tiredness/sleepiness; and (4) the Tiredness Symptoms Scale (TSS), a 14 items check list. Each test session lasted for 8 min, followed by a 12 min pause. The level and time course of cognitive performance and self-rating data were analysed with hierarchical linear mixed effects models. Cognitive tests showed decrements in alertness and selective attention in untreated patients with insomnia, narcolepsy, and sleep apnea. Narcoleptic patients and untreated OSA had a lower CFF threshold than controls, and for narcoleptic patients the time course differed from that of all other groups. In the visual tracking test the performance of all groups of patients was worse compared with normal controls. Self-rated tiredness/sleepiness was significantly more pronounced in the three groups of untreated patients than in control subjects.
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PMID:Daytime variation in performance and tiredness/sleepiness ratings in patients with insomnia, narcolepsy, sleep apnea and normal controls. 1556 Jul 72

Without specific etiology or effective treatment, chronic fatigue syndrome (CFS) remains a contentious diagnosis. Individuals with CFS complain of fatigue and poor sleep--symptoms that are often attributed to psychological disturbance. To assess the nature and prevalence of sleep disturbance in CFS and to investigate the widely presumed presence of psychological maladjustment we examined sleep quality, sleep disorders, physical health, daytime sleepiness, fatigue, and psychological adjustment in three samples. individuals with CFS; a healthy control group; and individuals with a definite medical diagnosis: narcolepsy. Outcome measures included physiological evaluation (polysomnography), medical diagnosis, structured interview, and self-report measures. Results indicate that the CFS sample had a very high incidence (58%) of previously undiagnosed primary sleep disorder such as sleep apnea/hypopnea syndrome and restless legs/periodic limb movement disorder. They also had very high rates of self-reported insomnia and nonrestorative sleep. Narcolepsy and CFS participants were very similar on psychological adjustment: both these groups had more psychological maladjustment than did control group participants. Our data suggest that primary sleep disorders in individuals with CFS are underdiagnosed in primary care settings and that the psychological disturbances seen in CFS may well be the result of living with a chronic illness that is poorly recognized or understood.
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PMID:Sleep quality and psychological adjustment in chronic fatigue syndrome. 1566 45

Drowsiness and sleeping at the wheel are now identified as the reasons behind fatal crashes and highway accidents caused by occupational drivers. For many years, fatigue has been associated to risk of accidents but the causes of this symptom were unclear. Extensive or nocturnal driving was associated to accidents but few reports differentiated fatigue from sleepiness. In the early nineties, epidemiological data started investigating sleepiness and sleep deprivation as cause of accidents. Sleepiness at the wheel, sleep restriction and nocturnal driving have been incriminated in 20% of traffic accidents. Drugs affecting the central nervous system (i.e., narcotic analgesics, antihistamine drugs), nocturnal breathing disorders and narcolepsy have been also associated with an increasing risk of accidents. Treatments improving daytime vigilance (i.e., nasal Continuous Positive Airway Pressure) reduce significantly the risk of traffic accidents for a reasonable economical cost. Sleep disorders among occupational drivers need to be systematically investigated. Chronic daytime sleepiness is still under diagnosed and sleep disorders (i.e. obstructive sleep apnea syndrome) are not enough explored and treated in this exposed population of sedentary males. Drivers education and work schedules integrating notions of sleep hygiene as well as promotion of sleep medicine could significantly improve road safety.
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PMID:Sleepiness of occupational drivers. 1573 1

Sleep disorders are pervasive in patients with multiple sclerosis (MS) although clinically underrecognized by most physicians. The most common sleep disorders seen in patients with MS include insomnia, nocturnal movement disorders, sleep-disordered breathing, narcolepsy, and rapid eye movement sleep behavior disorder. Factors that influence the quality of sleep in this patient population include pain, nocturia, depression, medication effect, location of lesions, and disease severity. Disrupted sleep has the potential to cause daytime somnolence, increased fatigue, and nonrefreshing sleep, and it may be associated with dangerous respiratory events. Awareness and treatment of these conditions is vital to improving health and quality of life in patients with MS.
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PMID:Sleep disorders in multiple sclerosis. 1579 38

We used a self-report questionnaire to identify outpatients with chronic symptoms of sleep disorders and/or high pretest probability for sleep apnea as well as for restless legs syndrome (RLS), insomnia, and narcolepsy. Surveys were presented to patients waiting for an appointment in Veterans Administration (VA) Medical Center clinics in Northeast Ohio, USA. Items addressed the frequency of snoring behavior; wake time sleepiness or fatigue and history of obesity/hypertension for high risk for sleep apnea (Netzer et al. 1999), along with other symptoms, were scored as positive vs negative risk for insomnia, narcolepsy, and RLS. Of the patients offered the surveys, 886 (59.2%) provided timely responses to the questionnaire. Mean age was 62.5 years (range, 19 to 85 years); 95% were males; mean body mass index was 29.3 kg/cm(2) (range, 15.1 to 57.5 kg/cm(2)); and mean Epworth Sleepiness Scale score was 8.3 (range, 1 to 22) with 4.6% having a score >17. Of the respondents, 47.4% met high-risk criteria for sleep apnea, 41.7% for insomnia, 19% for restless leg syndrome, and 4.7% for narcolepsy. Twenty-four percent reported use of sleeping pills or bedtime alcohol. Drowsy driving >3-4 days a week or every day was reported in 5.7%. VA primary care patients have high prevalence for pretest probability for sleep apnea. This population also reports chronic symptoms for other sleep disorders and for drowsy driving.
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PMID:Sleep problems and the risk for sleep disorders in an outpatient veteran population. 1587 29

Interleukin-6 (IL-6) is a pleiotropic cytokine produced by numerous types of immune and nonimmune cells and is involved in many pathophysiologic mechanisms in humans. Many studies suggest that IL-6 is a putative 'sleep factor' and its circadian secretion correlates with sleep/sleepiness. IL-6 is elevated in disorders of excessive daytime sleepiness such as narcolepsy and obstructive sleep apnea. It correlates positively with body mass index and may be a mediator of sleepiness in obesity. Also the secretion of this cytokine is stimulated by total acute or partial short-term sleep loss reflecting the increased sleepiness experienced by sleep-deprived individuals. Studies that evaluated the 24-hour secretory pattern of IL-6 in healthy young adults suggest that IL-6 is secreted in a biphasic circadian pattern with two nadirs at about 08.00 and 21.00, and two zeniths at about 19.00 and 05.00 h. In contrast, following sleep deprivation or in disorders of sleep disturbance, e.g., insomnia, IL-6 peaks during the day and, based on the level of stress system activity, i.e., cortisol secretion, contributes to either sleepiness and deep sleep (low cortisol) or feelings of tiredness and fatigue and poor sleep (high cortisol). In order to address concerns about the potential impact of differences of IL-6 levels between the beginning and the end of the 24-hour blood-drawing experiment, we proceeded with a cosinor analysis of 'detrended' data in young and old healthy individuals. This new analysis did not affect the biphasic circadian pattern of IL-6 secretion in young adults, while it augmented the flattened circadian pattern in old individuals in whom the difference was greater. Finally, IL-6 appears to be somnogenic in rats and exhibits a diurnal rhythm that follows the sleep/wake cycle in these animals. We conclude that IL-6 is a mediator of sleepiness and its circadian pattern reflects the homeostatic drive for sleep.
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PMID:IL-6 and its circadian secretion in humans. 1590 20

Narcolepsy is a syndrome of unknown aetiology characterised by excessive daytime sleepiness (often severe) usually in association with cataplexy (brief episodes of partial or complete muscle paralysis) and often with other uncommon symptoms. Due to limited disease-specific knowledge, medication treatment for this condition has focussed on specific symptom amelioration rather than improving or eliminating underlying disease mechanisms. Such treatment generally consists of stimulants for daytime sleepiness and anticataplectic medication for cataplexy; hence, both types of agents are reviewed in this article. Recent discoveries, including the finding that canine familial narcolepsy is caused by a single gene defect in the hypocretin receptor, coupled with the findings in human narcoleptics of undetectable hypocretin levels in the CSF and of severe hypocretin-containing neuronal atrophy in brains of deceased narcoleptics, have shifted the focus of narcolepsy treatment research to the hypocretin system. The hope is that a single agent can be developed to provide effective treatment for all symptoms of narcolepsy. While the mechanism of action in narcolepsy is unknown, gamma-hydroxybutyrate (GHB) is proving to be such an agent. Interestingly, GHB is not known to impact hypocretin pathways in the brain, yet specific research exploring this possible interaction has not been performed. The market for medications limited to use by narcoleptics is small because of the relatively low prevalence of narcolepsy; however, the prevalence of clinically important daytime sleepiness and/or fatigue is surprisingly high. New agents that effectively manage the sleepiness of narcolepsy thus have a much larger potential for appropriate use in treating sleepiness and fatigue in the general population. This fact has recently been demonstrated by the tremendous success of modafinil, a drug introduced to the market a little over 2 years ago, which was developed to treat sleepiness in narcolepsy but now is used in a much larger patient population.
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PMID:Medications for the treatment of narcolepsy. 1598 24

Acute infection is known to perturb psycho-neuroendocrine-immune (PNI) gene expression. Oligonucleotide microarrays were used to examine PNI gene expression in the peripheral blood of 13 subjects with infectious mononucleosis (IM). Novel peripheral blood gene expression activity was correlated with central-nervous-system-mediated symptoms including fatigue and sleep disturbance. Of note, expression of the MADS box transcription enhancer factor 2 polypeptide C (MEF2C) gene, previously implicated in skeletal muscle myogenesis, correlated with symptoms of musculo-skeletal pain and fatigue. Expression of the hypocretin/orexin receptor HCRTR2, which has been implicated in narcolepsy, correlated with sleep disturbance. And, VACHT, the vesicular acetylcholine transporter, was highly correlated with neurocognitive disturbance. The expression of both HCRTR2 and MEF2C in the peripheral blood was validated by reverse transcription PCR. Thus, investigation of the PNI response in peripheral blood may provide novel insights into the complex pathophysiology of centrally mediated disease states.
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PMID:Correlation of psycho-neuroendocrine-immune (PNI) gene expression with symptoms of acute infectious mononucleosis. 1637 18

Sleep-related disturbed breathing and parasomnia in very young children are in the focus of epidemiological interest. The cardinal symptom, i.e. snoring, in connection with nocturnal perspiration, mouth breathing, susceptibility to infection of the upper respiratory tract and tiredness during the day or hypermotility, can be an indication of obstructive sleep apnea (OSA). The common treatment is adenotomy unless there is indication of allergic swelling of the nasal mucous membrane. Other anatomic predispositions for OSA must be considered (tonsillar hypertrophy, midfacial hypoplasia, micro- and retrognathia, e.g. in patients with Down's syndrome or patients with preoperated cleft lip face palate). Inhalative nasal corticoids are a possible alternative to adenotomy in light to medium grade cases of OSA. Tonsillotomy is indicated only in serious OSA cases, tonsillectomy is only justified in cases of chronic tonsillitis or more than 4-6 cases of angina in the last 12 months. Treatment with nasal CPAP is tolerated well also in childhood. Patients with central hypoventilation syndromes, insufficiency of the respiratory musculature or obesitas hypoventilation syndrome can usually be ventilated by non-invasive approach using a nasal mask. Patients suffering from parasomnia should always be asked if they snore at night because if OSA is diagnosed and treated, there are very good prospects of curing somnambulism as well. Like with narcolepsy and REM sleep, a close HLA association has also been identified for family somnambulism. In cases of parasomnia which becomes manifest only after very young age frontal lobe epilepsy should be suspected and searched by polysomnographic and simultaneous continuous nocturnal video surveillance. If reversive development or unclear motoric and utterance phenomena are observed, sleep-bound convulsive disorder should be looked for. Syncopal events can require comprehensive cardiological diagnosis, including exclusion of nightly disorders of the cardiac rhythm.
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PMID:[Sleep disorders in infancy--aspects of diagnosis and somatic background]. 1649 23


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