Sleep, neuroimmune and neuroendocrine functions in fibromyalgia and chronic fatigue syndrome

Abstract:

The justification for disordered chronobiology for fibromyalgia and chronic fatigue syndrome (CFS) is based on the following evidence: The studies on disordered sleep physiology and the symptoms of fibromyalgia and CFS; the experimental studies that draw a link between interleukin-1 (IL-1), immune-neuroendocrine-thermal systems and the sleep-wake cycle; studies and preliminary data of the inter-relationships of sleep-wakefulness, IL-1, and aspects of peripheral immune and neuroendocrine functions in healthy men and in women during differing phases of the menstrual cycle; and the observations of alterations in the immune-neuroendocrine functions of patients with fibromyalgia and CFS (Moldofsky, 1993b, d). Time series analyses of measures of the circadian pattern of the sleep-wake behavioural system, immune, neuroendocrine and temperature functions in patients with fibromyalgia and CFS should determine whether alterations of aspects of the neuro-immune-endocrine systems that accompany disordered sleep physiology result in nonrestorative sleep, pain, fatigue, cognitive and mood symptoms in patients with fibromyalgia and CFS.

 

Source: Moldofsky H. Sleep, neuroimmune and neuroendocrine functions in fibromyalgia and chronic fatigue syndrome. Adv Neuroimmunol. 1995;5(1):39-56. http://www.ncbi.nlm.nih.gov/pubmed/7795892

 

Alpha-delta sleep in patients with a chief complaint of chronic fatigue

Abstract:

Our prospective, standardized cohort study was designed to assess the presence of alpha wave intrusions during non-rapid eye movement sleep (alpha-delta sleep) and its relationship to fibromyalgia, major depression, and chronic fatigue syndrome (CFS) in patients with a chief complaint of chronic fatigue.

The study group comprised 30 consecutive patients seen at a university hospital referral clinic for evaluation of chronic fatigue. All patients had nocturnal polysomnography, dolorimetric tender point assessment for fibromyalgia, a comprehensive history, physical, and laboratory evaluation, and a structured psychiatric interview. Alpha-delta sleep was identified in 8 of the 30 patients (26%), major depression in 20 (67%), CFS in 15 (50%), and fibromyalgia in 4 (13%). Ten of the 30 patients (33%) had a primary sleep disorder (sleep apnea, periodic limb movements, or narcolepsy).

Alpha-delta sleep was not significantly correlated with fibromyalgia, CFS, major depression, or primary sleep disorders, but was significantly more common among patients who had chronic fatigue without major depression. We conclude that primary sleep disorders are relatively common among patients with chronic fatigue and must be diligently sought and treated. Alpha-delta sleep is not a marker of fibromyalgia or CFS, but may contribute to the illness of nondepressed patients with these conditions.

Comment in: Sleep disorders and chronic fatigue. [South Med J. 1994]

 

Source: Manu P, Lane TJ, Matthews DA, Castriotta RJ, Watson RK, Abeles M. Alpha-delta sleep in patients with a chief complaint of chronic fatigue. South Med J. 1994 Apr;87(4):465-70. http://www.ncbi.nlm.nih.gov/pubmed/8153772

 

Sleep disorders in patients with chronic fatigue

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.

 

Source: Buchwald D, Pascualy R, Bombardier C, Kith P. Clin Infect Dis. 1994 Jan;18 Suppl 1:S68-72. http://www.ncbi.nlm.nih.gov/pubmed/8148456

 

Insomnia in the chronic fatigue syndrome

Editor,-Iain Duncan is mistaken in his assertion that the results of our study of patients with the chronic fatigue syndrome can be explained by daytime dozing. According to data from the diaries kept by the subjects in the study, the patients with the chronic fatigue syndrome slept for a mean of 11 minutes during the day and the healthy controls for 0 minutes. There was no association between either the time spent asleep or the time spent resting in bed during the day and the presence of any sleep disorder (or the time spent awake after the onset of sleep at night) in the patients with the chronic fatigue syndrome or the normal controls. Furthermore, in the few patients with the syndrome who wore their polysomnograph for the whole 24 hours there was no association between time spent asleep during the day and the time spent awake after the onset of sleep.

You can read the rest of this comment here: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1678179/pdf/bmj00031-0056a.pdf

 

Source: Morriss R. Insomnia in the chronic fatigue syndrome. BMJ. 1993 Jul 24;307(6898):264. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1678179/

 

ABC of sleep disorders. Sleep problems in patients with medical illness

Sleep complaints are ubiquitous in patients with medical illness. A recent survey of outpatients attending hospital clinics indicated that the vast majority of patients reported sleep disruption concomitant with their condition. The proportion with complaints (> 70%) was more than twice that among control subjects. Doctors rarely ask about sleep problems in the context of medical illness despite the fact that the patient’s first complaint disruption of sleep architecture in may be that a particular symptom caused sleep disruption.

There are specific reasons for sleep disruptions in patients with medical illness-for example, people are often deprived of sleep before an operation. Polysomnography has shown that there is a preoperative of sleep) reduction in slow wave sleep and that this is related to the anticipated importance of surgery. The increase in deep sleep that occurs after an operation is thought to facilitate the healing process.

A variety of sleep variables may be influenced by specific disorders and each of these effects is likely to differ. A decrease in deep (slow wave) sleep, for example, may lead to a sensation of having low energy, whereas repeated interruption of sleep may lead to daytime sleepiness.

Drugs may also disrupt sleep architecture by suppressing rapid eye movement (REM) sleep or by causing a withdrawal effect during the night. In both cases the drug clearly alters sleep, but the impact on health and recovery may differ.

Fatigue is common in several medical conditions. Clinicians, researchers, and patients themselves claim that the fatigue experienced in certain medical conditions differs qualitatively from the experience of tiredness or sleepiness. However, there have been few attempts to separate these states. In this article we provide an overview of the impact of medical disorders on sleep.

You can read the rest of this article here: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1677972/pdf/bmj00023-0050.pdf

 

Source: Shapiro CM, Devins GM, Hussain MR. ABC of sleep disorders. Sleep problems in patients with medical illness. BMJ. 1993 Jun 5;306(6891):1532-5. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1677972/

 

Abnormalities of sleep in patients with the chronic fatigue syndrome

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.

 

Source: Morriss R, Sharpe M, Sharpley AL, Cowen PJ, Hawton K, Morris J. Abnormalities of sleep in patients with the chronic fatigue syndrome. BMJ. 1993 May 1;306(6886):1161-4. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1677618/ (Full article)

 

Pharmacological approaches to the therapy of chronic fatigue syndrome

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.

 

Source: McCluskey DR. Pharmacological approaches to the therapy of chronic fatigue syndrome. Ciba Found Symp. 1993;173:280-7; discussion 287-97. http://www.ncbi.nlm.nih.gov/pubmed/8491103

 

Fibromyalgia, sleep disorder and chronic fatigue syndrome

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.

 

Source: Moldofsky H. Fibromyalgia, sleep disorder and chronic fatigue syndrome. Ciba Found Symp. 1993;173:262-71; discussion 272-9. http://www.ncbi.nlm.nih.gov/pubmed/8491102

 

Chronic fatigue and chronic fatigue syndrome: clinical epidemiology and aetiological classification

Abstract:

To determine the medical and psychiatric diagnoses that have an aetiological role in chronic fatigue we conducted a prospective study of 405 (65% women) patients who presented for evaluation with this chief complaint to an academic medical centre.

The average age was 38.1 years and the average duration of fatigue at entry in the study was 6.9 years. All patients were given comprehensive physical and laboratory evaluations and were administered a highly structured psychiatric interview. Psychiatric diagnoses explaining the chronic fatigue were identified in 74% of patients and physical disorders were diagnosed in 7% of patients.

The most common psychiatric conditions in this series were major depression, diagnosed in 58% of patients, panic disorder, diagnosed in 14% of patients, and somatization disorder, diagnosed in 10% of patients. Primary sleep disorders, diagnosed in 2% patients, and chronic infections, confirmed in 1.6% patients, explained the majority of cases whose chronic fatigue was attributed to a physical disorder.

Thirty per cent of patients met the criteria used to define the chronic fatigue syndrome (CFS). Compared with age- and gender-matched control subjects with chronic fatigue, CFS patients had a similarly high prevalence of current psychiatric disorders (78% versus 82%), but were significantly more likely to have somatization disorder (28% versus 5%) and to attribute their illness to a viral infection (70% versus 33%).

We conclude that most patients with a chief complaint of chronic fatigue, including those exhibiting the features of CFS, suffer from standard mood, anxiety and/or somatoform disorders. Careful research is still needed to determine whether CFS is a distinct entity or a variant of these psychiatric illness.

 

Source: Manu P, Lane TJ, Matthews DA. Chronic fatigue and chronic fatigue syndrome: clinical epidemiology and aetiological classification. Ciba Found Symp. 1993;173:23-31; discussion 31-42. http://www.ncbi.nlm.nih.gov/pubmed/8491100

 

Neuro-psychiatric aspects of chronic fatigue syndrome

Abstract:

Chronic fatigue syndrome (CFS) is easily differentiated from various neurological organic disorders by conventional clinical examinations. The most important disease for distinguishment from CFS is fibromyalgia syndrome, in which the prominent and cardinal feature is a deprivation of stage 4 slow wave sleep.

Experimentally, the sleep disturbance in controls can induce general myalgia, muscle tender points, severe fatigue and stiffness on awakening. The EEG abnormality is slow alpha wave contaminants on slow wave background, which is identical to EEG of CFS. The results clearly imply that CFS is not a hysterical or psychogenic disease, and that fibromyalgia may be a central fundamental of CFS.

Fibromyalgia, however, has distinct features such as no antecedent inflammatory process and no endemics. Therefore, the syndrome has features distinct from, in addition to common features to CFS. It is also very difficult to distinguish CFS from depression. The above-mentioned features can be observed in depression. Now, study of brain blood flow or metabolism by PET or SPECT can be a possible tool for establishment of the CFS identity.

 

Source: Shimizu T. Neuro-psychiatric aspects of chronic fatigue syndrome. Nihon Rinsho. 1992 Nov;50(11):2630-4. [Article in Japanese] http://www.ncbi.nlm.nih.gov/pubmed/1287239