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

 

Vestibular function test anomalies in patients with chronic fatigue syndrome

Abstract:

Chronic fatigue syndrome (CFS) is distinguished by the new onset of debilitating fatigue that lasts at least 6 months, concomitant with other symptoms to be described later. Many CFS patients complain of disequilibrium, yet the exact type of the balance dysfunction and its function and its location (peripheral vs. central) have not been described.

Herein we report results of vestibular function testing performed on 11 CFS patients. These results revealed no predominant pattern of abnormalities. Patients typically performed below average in dynamic posturography testing, with a significant number of falls in the tests requiring subjects to depend heavily on the vestibular system. One patient had abnormal caloric testing, while 3 had abnormally low earth vertical axis rotation (EVA) gains at the higher frequencies tested.

As a group, the average gain of EVA was significantly lower than normals in the 0.1 – 1.0 Hz range (p < 0.05). In earth horizontal axis rotation, the CFS group had a higher than normal bias value for the optokinetic (OKN) and eyes open in the dark conditions (p < 0.05), but had normal scores during visual vestibular reflex testing. Five of the 11 subjects had an abnormal OKN bias build up over the course of the run, equal to or actually exceeding the 60 degrees/s target velocity by as much as 14 degrees/s.

Altogether, these results are more suggestive of central nervous system deficits than of peripheral vestibular disfunction.

 

Source: Ash-Bernal R, Wall C 3rd, Komaroff AL, Bell D, Oas JG, Payman RN, Fagioli LR. Vestibular function test anomalies in patients with chronic fatigue syndrome. Acta Otolaryngol. 1995 Jan;115(1):9-17. http://www.ncbi.nlm.nih.gov/pubmed/7762393

 

The impact of catastrophic beliefs on functioning in chronic fatigue syndrome

Abstract:

This study investigated the association between catastrophic beliefs and disability in the context of Chronic fatigue syndrome (CFS). A sample of 282 CFS sufferers were asked about the consequences of pushing themselves beyond their present physical state. Responses were coded into catastrophic or non-catastrophic categories. While not differing on the length of illness or psychological adjustment, subjects demonstrating catastrophic responses evidenced significantly higher levels of fatigue and were more disabled in terms of their ability to work both in their normal occupation and around the house. Catastrophizers also showed greater disability in terms of their sleep and rest, social communication, and recreational activities. The role of catastrophic beliefs and personal perceptions of CFS in maintaining the illness is discussed.

 

Source: Petrie K, Moss-Morris R, Weinman J. The impact of catastrophic beliefs on functioning in chronic fatigue syndrome. J Psychosom Res. 1995 Jan;39(1):31-7. http://www.ncbi.nlm.nih.gov/pubmed/7760301

 

Correlates of somatic causal attributions in primary care patients with fatigue

Abstract:

Researchers in the field of chronic fatigue in tertiary care found that patients’ somatic (e.g. viral) explanations for their condition may lead to chronicity of symptoms. We studied the influence of a somatic attributional bias on outcome and reported symptoms in primary care patients with fatigue.

We compared fatigue scores on a specific scale, and number of presented symptoms, in two groups of primary care patients with ‘functional’ fatigue: 75 with a high score on the somatic subscale of the Fatigue Attribution Scale (S-FAS), and 95 with a low score on the S-FAS. At the index visit, patients with low and high scores on the S-FAS were not different for age, sex, fatigue scores, and levels of depressive symptoms.

Patients with high scores on the S-FAS presented significantly more somatic and psychological symptoms-a total of 36 symptoms for 24 patients (25.3%) in the low-score group, and a total of 52 symptoms for 31 patients (41.3%) in the high-score group.

Forty-two days later, at the follow-up visit, the fatigue scores were similar in both groups. In primary care patients with fatigue not due to somatic illness or major depression, the tendency to attribute fatigue to somatic causes is not associated with a worse outcome, but with a higher number of reported symptoms.

 

Source: Cathébras P, Jacquin L, le Gal M, Fayol C, Bouchou K, Rousset H. Correlates of somatic causal attributions in primary care patients with fatigue. Psychother Psychosom. 1995;63(3-4):174-80. http://www.ncbi.nlm.nih.gov/pubmed/7624463

 

Chronic fatigue syndrome. 1: Etiology and pathogenesis

Abstract:

Chronic fatigue syndrome (CFS) is a disorder of unknown etiology characterized by debilitating fatigue and other somatic and neuropsychiatric symptoms. A range of heterogeneous clinical and laboratory findings have been reported in patients with CFS. Various theories have been proposed to explain the underlying pathophysiologic processes but none has been proved.

Research findings of immunologic dysfunction and neuroendocrine changes suggest the possible dysregulation of interactions between the nervous system and the immune system. Without a clear understanding of its etiopathogenesis, CFS has no definitive treatment.

Management approaches have been necessarily speculative, and they have evolved separately in a number of medical and nonmedical disciplines. The results of several controlled treatment studies have been inconclusive. An accurate case definition identifying homogeneous subtypes of CFS is needed. The integration of medical and psychologic treatment modalities and the use of both biologic and psychologic markers to evaluate treatment response will enhance future treatment strategies.

 

Source: Farrar DJ, Locke SE, Kantrowitz FG. Chronic fatigue syndrome. 1: Etiology and pathogenesis. Behav Med. 1995 Spring;21(1):5-16. http://www.ncbi.nlm.nih.gov/pubmed/7579775

 

Post-hepatitis syndrome revisited

Abstract:

To examine the role of acute hepatitis A and B infection in the aetiology of chronic fatigue syndrome and psychiatric morbidity we studied 40 patients with acute viral hepatitis A or B consecutively admitted to an infectious diseases unit and studied at least 6 months after recovery.

Liver function tests (LFT) had returned to normal in each case. Forty-seven patients with other infectious diseases, of which 12 were presumed viral, admitted immediately after each hepatitis patient during the same period acted as controls. The main outcome measures were scores on a fatigue and muscle pain questionnaire, general health questionnaire (GHQ-12) and supplementary questions.

The hepatitis cases scored significantly higher fatigue scores, GHQ-12 scores and muscle pain scores. Length of time since recovery from illness, age and sex were not confounding factors. Hepatitis cases were also less energetic, had greater weight change, had altered alcohol tolerance, had less exercise tolerance and felt less fit than the control group and compared with their premorbid state.

Hence fatigue is more common after recovery in patients hospitalized for hepatitis A and B up to 30 months post-infection compared with matched controls hospitalized for other infectious diseases. Hepatitis A and B infection is a risk factor for post-infection fatigue, intermittent fatigue, as well as for psychiatric morbidity.

 

Source: Berelowitz GJ, Burgess AP, Thanabalasingham T, Murray-Lyon IM, Wright DJ. Post-hepatitis syndrome revisited. J Viral Hepat. 1995;2(3):133-8. http://www.ncbi.nlm.nih.gov/pubmed/7493307

 

The chronic fatigue syndrome: a comprehensive approach to its definition and study. International Chronic Fatigue Syndrome Study Group

Abstract:

The complexities of the chronic fatigue syndrome and the methodologic problems associated with its study indicate the need for a comprehensive, systematic, and integrated approach to the evaluation, classification, and study of persons with this condition and other fatiguing illnesses. We propose a conceptual framework and a set of guidelines that provide such an approach. Our guidelines include recommendations for the clinical evaluation of fatigued persons, a revised case definition of the chronic fatigue syndrome, and a strategy for subgrouping fatigued persons in formal investigations.

Comment in:

The chronic fatigue syndrome. [Ann Intern Med. 1995]

The chronic fatigue syndrome. [Ann Intern Med. 1995]

The chronic fatigue syndrome. [Ann Intern Med. 1995]

The chronic fatigue syndrome. [Ann Intern Med. 1995]

 

Source: Fukuda K, Straus SE, Hickie I, Sharpe MC, Dobbins JG, Komaroff A. The chronic fatigue syndrome: a comprehensive approach to its definition and study. International Chronic Fatigue Syndrome Study Group. Ann Intern Med. 1994 Dec 15;121(12):953-9. http://www.ncbi.nlm.nih.gov/pubmed/7978722

 

Chronic fatigue syndrome and fibromyalgia

Comment on: Population study of tender point counts and pain as evidence of fibromyalgia. [BMJ. 1994]

 

EDITOR,-The relation between muscle pain, tender points, the chronic fatigue syndrome, and fibromyalgia are complex, and simplistic answers are inappropriate. In their paper Peter Croft and colleagues extrapolate their results to make two statements that I believe to be incorrect.’

My conclusions are based on 100 consecutive patients seen at Raigmore Hospital NHS Trust, who fulfilled precise definitions of the chronic fatigue syndrome 2 or fibromyalgia.3 The importance of this definition of the syndrome is that it has the same three month cut off for length of illness as fibromyalgia.3 Of the 100 patients, 99 (74 women, 25 men) had the chronic fatigue syndrome and one (a woman) had fibromyalgia. Of the patients with the chronic fatigue syndrome, 63 had muscle pain and 28 had tender points on examination, 23 had both, and five had no muscle pain but tender points. These results do not support the authors’ statement that the reason why fibromyalgia is not more common in Britain has been the acceptability of the chronic fatigue syndrome as an alternative diagnosis.

The authors also say that it is “inappropriate to define an entity as fibromyalgia.” As a clinical virologist, I strongly disagree with this as the distribution and number of tender points in fibromyalgia are different from those in the chronic fatigue syndrome, and the management of the two conditions is different.4 Patients with the syndrome should be advised not to increase their activities gradually until they feel 80% of normal,5 whereas patients with fibromyalgia may benefit from a regimen of increasing activity.4

You can read the rest of this comment here: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2541601/pdf/bmj00468-0067b.pdf

 

Source: Ho-Yen DO. BMJ. Chronic fatigue syndrome and fibromyalgia. 1994 Dec 3;309(6967):1515. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2541601/

 

Immunological abnormalities in patients with chronic fatigue syndrome

Abstract:

Between January 1991 and January 1993, 265 patients who fulfilled the CDC criteria of the working case definition of Chronic Fatigue Syndrome (CFS) have been observed at our Institution and submitted for clinical and laboratory evaluation.

One hundred and sixty-three patients were females and 102 males, the median age was 35 years (range 4-55 years); all patients reported profound and prolonged fatigue, lasting for a median of 3 years (range 6 months-10 years), preceded or accompanied at appearance by fever in 185 cases, and neuropsychologic problems including inability to concentrate, difficulty in thinking, confusion, irritability, forgetfulness, and depression. The fatigue was so severe that it required 102 patients to stop their working activities for a period of time ranging from 3 months to 2 years (range 7 months).

In 40 consecutive patients a comprehensive immunologic testing by single and two-colour flow cytometry was performed and results compared with a group of 35 healthy, age- and sex-matched controls. Whilst no significant differences were found in the absolute numbers of circulating total T cells (CD3+) and of total helper/inducer (CD4+) or suppressor/cytotoxic (CD8+) T cells, an evident reduction in CD3-/CD16+ and CD57+/CD56+ NK lymphocytes along with an expansion of the CD8+/CD56+ and CD16-/CD56+ NK subsets, were found in the CFS group.

In addition, CD56+ NK cells from CFS subjects were found to express an increased amount of cell adhesion molecules (CD11b, CD11c, CD54) and activation antigens (CD38). Both the percentage and absolute numbers of CD4+ T cells bearing the CD45RA antigen appeared significantly reduced in CFS patients, and CD4+ T lymphocytes from CFS subjects displayed an increased expression of the intercellular adhesion molecule-1 (ICAM-1/CD54).

Finally, the total numbers of circulating (CD19+) B lymphocytes, were significantly higher in CFS cases than in controls, and in 11 out of 30 CFS patients the increase in circulating B cells was sustained by the expansion of the CD5+/CD19+ subset of B lymphocytes.

We conclude that CFS is a syndrome not previously described in Italy, with already known clinical characteristics and appears to be associated with several immunologic abnormalities, including those reported previously in cohort of patients from different countries. We also show for the first time that CD56- NK cell subsets from CFS patients display an abnormally increased expression of cell adhesion molecules and activation markers.

 

Source: Tirelli U, Marotta G, Improta S, Pinto A. Immunological abnormalities in patients with chronic fatigue syndrome. Scand J Immunol. 1994 Dec;40(6):601-8. http://www.ncbi.nlm.nih.gov/pubmed/7997849

 

Sympathetic overactivity in subjects complaining of unexplained fatigue

Abstract:

Theoretical and practical considerations suggest that in subjects complaining of fatigue, in the absence of evident organ dysfunction, an alteration in the autonomic nervous system might be present as a functional correlate.

Autoregressive spectral analysis of R-R interval variability from a surface ECG, was used in healthy control subjects (n = 24, age 45 +/- 4 years) and in subjects complaining of unexplained fatigue (n = 53, age 46 +/- 9 years) to obtain quantitative indices of the state of the sympathovagal balance, both at rest and during a mental stimulus (mental arithmetic), capable of enhancing sympathetic drive. Sympathetic and vagal modulations were inferred from the normalized powers of the low frequency and high frequency spectral components respectively.

We observed in patients, at rest, a prevailing low frequency component of R-R variability (patients low frequency = 73 +/- 11, control subjects 51 +/- 10 normalized units, P < 0.05). The responsiveness to mental arithmetic was reduced in patients as compared with controls. Systolic blood pressure variability did not differ. This suggested a selective imbalance in autonomic control of the sinoatrial node, characterized by sympathetic predominance as well as by vagal withdrawal, at rest.

The possibility of discriminating patients from control subjects on the basis of simple non-invasive functional markers might provide a better understanding of the mechanisms, clinical evolution and outcome of conditions such as the chronic fatigue syndrome, which lack ordinary evidence of disease, but comprise, as physiopathological correlate, a quantitative alteration of autonomic control.

 

Source: Pagani M, Lucini D, Mela GS, Langewitz W, Malliani A. Sympathetic overactivity in subjects complaining of unexplained fatigue. Clin Sci (Lond). 1994 Dec;87(6):655-61. http://www.ncbi.nlm.nih.gov/pubmed/7874856