Sleep and CFS

Abstract: This prospective, cohort study examined the prevalence of sleep disorders among highly selected patients with chronic fatigue. On the basis of responses suggestive of sleep pathology on a screening questionnaire, 59 patients from a university-based clinic for chronic fatigue who had undergone a medical and psychiatric evaluation underwent polysomnography. Criteria for chronic fatigue syndrome (CFS) were met by 64% of patients and those for a current psychiatric disorder were met by 41%. Overall, 41% of patients had abnormal results for a multiple sleep latency test and 81% had at least one sleep disorder, most frequently sleep apnea (44%) and idiopathic hypersomnia (12%). In comparing patients who did and did not meet CFS criteria, no significant differences were found in individual sleep symptoms or sleep disorders. Likewise, symptoms and sleep disorders were unrelated to psychiatric diagnoses. In conclusion, chronically fatigued patients with suggestive symptoms may have potentially treatable coexisting sleep disorders that are not associated with meeting criteria for CFS or a current psychiatric disorder.

Fischler B, Le Bon O, Hoffmann G, Cluydts R, Kaufman L, De Meirleir K. Sleep anomalies in the chronic fatigue syndrome. A comorbidity study. Neuropsychobiology 1997; 35(3): 115-22.

Abstract: Polysomnographic findings were compared between a group of patients with the chronic fatigue syndrome (CFS; n = 49) and a matched healthy control (HC) group (n = 20). Sleep initiation and sleep maintenance disturbances were observed in the CFS group. The percentage of stage 4 was significantly lower in the CFS group. A discriminant analysis allowed a high level of correct classification of CFS subjects and HC. Sleep-onset latency and the number of stage shifts/hour contributed significantly to the discriminant function. The presence of these anomalies as well as the decrease in stage 4 sleep were not limited to the patients also diagnosed with fibromyalgia or with a psychiatric disorder. No association was found between sleep disorders and the degree of functional status impairment. The mean REM latency and the percentage of subjects with a shortened REM latency were similar in CFS and HC.

Return to Top

Gill J, Feldman NT. Sleep disorders and chronic fatigue [Letter]. Southern Medical Journal 1994; 87(12): 1289-90.

McCluskey DR. Pharmacological approaches to the therapy of chronic fatigue syndrome. Ciba Foundation Symposium 1993; 173: 280-7.

Abstract: Although a variety of pharmacological agents have been used to treat patients with chronic fatigue syndrome none has been shown to effect a complete resolution of symptoms. Data obtained from a retrospective study and from an objective assessment of the aerobic work capacity of patients with this disorder suggest that the underlying pathophysiological abnormality is a disorder of sleep regulation. This results not only in profound fatigue and lethargy but also reduced sensory threshold for pain, disordered temperature regulation, cardiovascular abnormalities, disturbed higher cerebral function and mental depression. Drugs which modulate sleep, such as tricyclic antidepressants, have a limited effect in improving the symptoms that CFS patients experience. We suggest that other agents which affect central nervous system neurotransmitters, particularly serotonin, may have potential in the management of this condition and need to be evaluated in large controlled clinical trials.

Moldofsky H. Fibromyalgia, sleep disorder and chronic fatigue syndrome. Ciba Foundation Symposium 1993; 173: 262-71.

Abstract: Various research studies show that the amalgam of disordered sleep physiology, chronic fatigue, diffuse myalgia, and cognitive and behavioural symptoms constitutes a non-restorative sleep syndrome that may follow a febrile illness, as in the chronic fatigue syndrome. Where rheumatic complaints are prominent such a constellation of disturbed sleep physiology and symptoms also characterizes the fibromyalgia disorder. In contrast to the chronic fatigue syndrome, fibromyalgia is associated with a variety of initiating or perpetuating factors such as psychologically distressing events, primary sleep disorders (e.g. sleep apnoea, periodic limb movement disorder) and inflammatory rheumatic disease, as well as an acute febrile illness. The chronic fatigue syndrome and fibromyalgia have similar disordered sleep physiology, namely an alpha rhythm disturbance (7.5-11 Hz) in the electroencephalogram (EEG) within non-rapid eye movement (NREM) sleep that accompanies increased nocturnal vigilance and light, unrefreshing sleep. Aspects of cytokine and cellular immune functions are shown to be related to the sleep-wake system. The evidence suggests a reciprocal relationship of the immune and sleep-wake systems. Interference either with the immune system (e.g. by a viral agent or by cytokines such as alpha-interferon or interleukin 2) or with the sleeping-waking brain system (e.g. by sleep deprivation) has effects on the other system and will be accompanied by the symptoms of the chronic fatigue syndrome.

Return to Top

Morriss R, Sharpe M, Sharpley AL, Cowen PJ, Hawton K, Morris J. Abnormalities of sleep in patients with chronic fatigue syndrome. British Medical Journal 1993; 306: 1161.

Abstract: - OBJECTIVE-To determine whether patients with the chronic fatigue syndrome have abnormalities of sleep which may contribute to daytime fatigue. DESIGN-A case-control study of the sleep of patients with the chronic fatigue syndrome and that of healthy volunteers. SETTING-An infectious disease outpatient clinic and subjects' homes. SUBJECTS-12 patients who met research criteria for the chronic fatigue syndrome but not for major depressive disorder and 12 healthy controls matched for age, sex, and weight. MAIN OUTCOME MEASURES-Subjective reports of sleep from patients' diaries and measurement of sleep patterns by polysomnography. Subjects' anxiety, depression, and functional impairment were assessed by interview. RESULTS-Patients with the chronic fatigue syndrome spent more time in bed than controls (544 min v 465 min, p < 0.001) but slept less efficiently (90% v 96%, p < 0.05) and spent more time awake after initially going to sleep (31.9 min v 16.6 min, p < 0.05). Seven patients with the chronic fatigue syndrome had a sleep disorder (four had difficulty maintaining sleep, one had difficulty getting to sleep, one had difficulty in both initiating and maintaining sleep, and one had hypersomnia) compared with none of the controls (p="0.003)." Those with sleep disorders showed greater functional impairment than the remaining five patients (score on general health survey 50.4% v 70.4%, p < 0.05), but their psychiatric scores were not significantly different. CONCLUSIONS-Most patients with the chronic fatigue syndrome had sleep disorders, which are likely to contribute to daytime fatigue. Sleep disorders may be important in the aetiology of the syndrome.

Morriss RK, Wearden AJ, Battersby L. The relation of sleep difficulties to fatigue, mood and disability in chronic fatigue syndrome. Journal of Psychosomatic Research 1997; 42(6): 597-605.

Abstract: The relationship of sleep complaints to mood, fatigue, disability, and lifestyle was examined in 69 chronic fatigue syndrome (CFS) patients without psychiatric disorder, 58 CFS patients with psychiatric disorder, 38 psychiatric out-patients with chronic depressive disorders, and 45 healthy controls. The groups were matched for age and gender. There were few differences between the prevalence or nature of sleep complaints of CFS patients with or without current DSM-IIIR depression, anxiety or somatization disorder. CFS patients reported significantly more naps and waking by pain, a similar prevalence of difficulties in maintaining sleep, and significantly less difficulty getting off to sleep compared to depressed patients. Sleep continuity complaints preceded fatigue in only 20% of CFS patients, but there was a strong association between relapse and sleep disturbance. Certain types of sleep disorder were associated with increased disability or fatigue in CFS patients. Disrupted sleep appears to complicate the course of CFS. For the most part, sleep complaints are either attributable to the lifestyle of CFS patients or seem inherent to the underlying condition of CFS. They are generally unrelated to depression or anxiety in CFS.

Return to Top

Sharpley A, Clements A, Hawton K, Sharpe M. Do patients with "pure" chronic fatigue syndrome (neurasthenia) have abnormal sleep? Psychosomatic Medicine 1997; 59(6): 592-596.

Abstract: OBJECTIVE: To determine whether patients with "pure" chronic fatigue syndrome (neurasthenia) have sleep abnormalities which may contribute to subjective measures of daytime fatigue. METHOD: Sleep characteristics of 20 patients meeting research criteria for chronic fatigue syndrome (CFS) but not depression, anxiety, or sleep disorder were compared with sleep characteristics of 20 healthy subjects matched for age and sex. Measures of sleep included a) subjective interview reports and sleep diaries and b) home-based polysomnography. RESULTS: Patients with CFS complained of poor quality unrefreshing sleep. They also napped during the day. Polysomnograph data showed no difference in actual nocturnal sleep time between the two groups although patients with CFS spent significantly longer in bed (p < .01), slept less efficiently (p < .03), and spent longer awake after sleep onset (p < .05). The polysomnographs of seven patients with CFS and one healthy subject were regarded as significantly abnormal. Five patients and one healthy subject had difficulty maintaining sleep. One patient had a disorder of both initiating and maintaining sleep and one patient woke early. CONCLUSIONS: Patients with "pure" CFS complain of unrefreshing sleep but only a minority have a clearly abnormal polysomnograph. The most common abnormality is of long periods spent awake after initial sleep onset. Although sleep abnormalities may play a role in the etiology of CFS, they seem to be unlikely to be an important cause of daytime fatigue in the majority of patients. However, pharmacological and behavioral methods that improve sleep quality may be an important component of a pragmatically based treatment package for patients who do have abnormal sleep.

Snorrason E, Geirsson A, Stefansson K. Trial of a selective acetylcholinesterase inhibitor, galanthamine hydrobromide, in the treatment of chronic fatigue syndrome. Journal of Chronic Fatigue Syndrome 1996; 2(2/3): 35-54.

Abstract: The purpose of the study was to search for a means of diminishing the plight of patients with chronic fatigue syndrome (CFS) and to test the hypothesis that central to the pathogenesis of CFS is a cholinergic defect. Forty-nine patients who fulfilled consensus criteria for CFS were treated with the acetylcholinesterase inhibitor, galanthamine hydrobromide. Thirtynine patients finsihed the study according to the protocol with 43% reporting 50% improvement whereas patients in the placebo group reported only 10% improvement in the same parameters of CFS. The improvement of patients on galanthamine was in most cases gradual and reached significance for the group only after four to eight weeks. The improvement was stable, and no patients who reported over 50% improvement on galanthamine relapsed to a pretrial level of any symptom. One of the most surprising effects was the dramatic improvement of sleep disturbances that occurred in most patients on this medication: more than 60% of the patients who finished the study reported over 70% improvement in sleep deficit. If the subjective report by patients can be proved by objective means, this would be the first demonstration of a drug that can be used to correct a sleep disturbance that also influences a specific stage in normal sleep. The most common adverse effect of galanthamine, as given in this study, was nausea that was dose-dependent and reversible. Galanthamine hydrobromide is relatively safe and appears to be an effective medication against many symptoms of CFS. But the positive results of this study have to be interpreted cautiously because of methodological limitations of this trial. First, this study was originally organized as a double-blind, placebo-controlled trial but was changed to an optional crossover after two weeks of treatment. Also, the adverse effects of the active drug in 30% of patients could compromise the double-blind. With these limitations in mind, it is nevertheless tempting to conclude that this study lends an indirect support to our hypothesis that a cholinergic deficit may play a role in the pathogenesis of the syndrome.

Whelton CL, Salit I, Moldofsky H. Sleep, Epstein-Barr Virus infection, musculoskeletal pain, and depressive symptoms in chronic fatigue syndrome. Journal of Rheumatology 1992; 19: 939-943.

Abstract: Sleep physiology, viral serology and symptoms of 14 patients with chronic fatigue syndrome (CFS) were compared with 12 healthy controls. All patients described unrefreshing sleep and showed a prominent alpha electroencephalographic nonrapid eye movement (7.5-11.0 Hz) sleep anomaly (p less than or equal to 0.001), but had no physiologic daytime sleepiness. There were no group differences in Epstein-Barr virus (EBV) antibody titers. The patient group had more fibrositis tender points (p less than 0.0001), described more somatic complaints (p less than 0.0001), and more depressive symptoms (p less than 0.0001). Patients with CFS do not show evidence for a specific chronic EBV infection, but show altered sleep physiology, numerous tender points, diffuse pain, and depressive symptoms. These features are similar to those found in fibromyalgia syndrome.

Latest News | Research | Information | Advocacy | Conference | Guidelines