Category: Pathophysiology

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

 

Immunity and the pathophysiology of chronic fatigue syndrome

Abstract:

The pathophysiology of chronic fatigue syndrome (CFS) remains unknown. The syndrome often follows a recognized or presumed infection and the disorder may therefore result from a disordered immune response to a precipitating infection or antigenic challenge.

Abnormalities of both humoral and cellular immunity have been demonstrated in a substantial proportion of patients with CFS. The most consistent findings are of impaired lymphocyte responses to mitogen and reduced natural killer cell cytotoxicity. Cutaneous anergy and immunoglobulin G subclass deficiencies have also been found.

Further studies are needed examining cytokine levels in serum and cerebrospinal fluid, and cytokine production in vitro in patients with CFS. Interpretation of the findings of published studies of immunity is limited by probable heterogeneity in the patient groups studied, and by the lack of standardization and reproducibility in the assays used.

The pattern of abnormalities reported in immunological testing in patients with CFS is consistent with the changes seen during the resolving phases of acute viral infection. These data provide circumstantial support for the hypothesis that CFS results from a disordered immune response to an infection. Longitudinal studies of immunity in patients developing CFS after defined infectious illnesses will provide the best means of further examining this hypothesis.

 

Source: Lloyd AR, Wakefield D, Hickie I. Immunity and the pathophysiology of chronic fatigue syndrome. Ciba Found Symp. 1993;173:176-87; discussion 187-92. http://www.ncbi.nlm.nih.gov/pubmed/8491097

 

Immunological and psychological dysfunction in patients receiving immunotherapy for chronic fatigue syndrome

Abstract:

Associations between immunological and psychological dysfunction in 33 patients with Chronic Fatigue Syndrome (CFS) were examined before and in response to treatment in a double blind, placebo-controlled trial of high dose intravenous immunoglobulin. Only those patients who received active immunotherapy demonstrated a consistent pattern of correlations between improvement in depressive symptoms and markers of cell-mediated immunity (CMI).

This finding lends some support to the hypothesis that depressive symptoms in patients with CFS occur secondary to, or share a common pathophysiology with, immunological dysfunction. This pattern and the lack of strong associations between depression and immunological disturbance prior to treatment are less supportive of the view that CFS is primarily a form of depressive disorder or that immunological dysfunction in patients with CFS is secondary to concurrent depression.

 

Source: Hickie I, Lloyd A, Wakefield D. Immunological and psychological dysfunction in patients receiving immunotherapy for chronic fatigue syndrome. Aust N Z J Psychiatry. 1992 Jun;26(2):249-56. http://www.ncbi.nlm.nih.gov/pubmed/1642616

 

Chronic fatigue syndrome and heterogeneity

Comment on: The measurement of fatigue and chronic fatigue syndrome. [J R Soc Med. 1992]

 

One thing which hampers medical research is a frustrating tendency for researchers to conclude that heterogeneous groups are homogeneous. Several examples can be cited including research into sudden infant death syndrome. In his editorial on chronic fatigue syndrome (CFS) Wessely (April 1992 JRSM, p 189) asserts that previous views suggesting CFS to be simply a form of somatized depression are no longer tenable because of one published and one unpublished study showing biological differences from major depression. This view is just as untenable as the notion that all CFS is depression. Surely the most likely explanation is that CFS represents a heterogeneous group. The notion that one or two positive findings exclude all other explanations is a dangerous one. Aside from the fact that it negates the possibility of heterogeneity it may have a tendency to narrow thinking on the subject, and this is, after all, the food for medical research.

You can read the full comment here: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1293669/pdf/jrsocmed00107-0092a.pdf

 

Source: Wright B. Chronic fatigue syndrome and heterogeneity. J R Soc Med. 1992 Sep;85(9):588. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1293669/

 

Chronic fatigue syndrome

Abstract:

Chronic Fatigue Syndrome appears to represent a spectrum of disorders in which a variety of pathophysiological mechanisms may operate. While the initiating event in the majority of patients is a pyrexial illness, possibly due to enterovirus infection, evidence of persisting infection or inflammatory changes in muscle and/or brain remain unconvincing.

CFS patients display a definite reduced aerobic work capacity compared to normal control subjects, but this may reflect a state of deconditioning resulting from prolonged physical inactivity. They also have an altered perception of their level of exertion and premorbid fitness.

The characteristic fluctuation in symptoms, with periods of relapses and partial remissions, may indicate that some central disorder of sensory perception is operational. It may be that a primary sleep disorder results in a reduced sensory threshold for afferent stimuli from muscle. This could well account for many of the subjective symptoms which patients experience. Much more research is clearly necessary if we are to achieve a better understanding of this distressing and at present enigmatic disorder.

 

Source: McCluskey DR, Riley MS. Chronic fatigue syndrome. Compr Ther. 1992 Apr;18(4):13-6. http://www.ncbi.nlm.nih.gov/pubmed/1628478

 

Unexplained fever and chronic fatigue: abnormal circadian temperature pattern

Abstract:

OBJECTIVES: Standard clinical and biological investigations can be used to determine the origin of persistent and moderate fever in a large number of otherwise asymptomatic patients. However, in a small proportion of cases, isolated fever and fatigue persist despite the absence of detectable organic malfunction. This study was conducted to investigate the circadian thermic pattern in patients with apparently unexplainable fever and chronic fatigue and in those with fever of recognized origin.

METHODS: We recorded central temperature continuously for 24 hours in patients with moderate fever of both unexplained and recognized origin, and in a control group of healthy volunteers. A Fourier series was used for harmonic analysis.

RESULTS: Thermic patterns specific to the three groups were identified by statistical and factorial analysis. The patients with fever of unknown origin and chronic fatigue were clearly characterized in terms of the phase, amplitude of the first (fundamental) harmonic and minimum circadian temperature.

CONCLUSION: The abnormal central temperature pattern in these patients may prove to be an important step in the management of febrile patients.

 

Source: Camus F, Henzel D, Janowski M, Raguin G, Leport C, Vildé JL. Unexplained fever and chronic fatigue: abnormal circadian temperature pattern. Eur J Med. 1992 Apr;1(1):30-6. http://www.ncbi.nlm.nih.gov/pubmed/1341974

 

Chronic tiredness and idiopathic chronic fatigue–a connection?

Abstract:

Evidence is adduced to support the proposal that pathological fatigue is a consequence of impaired capillary blood flow resulting in inadequate oxygen delivery, which is in accordance with physiological concepts of fatigue. Case reports are presented.

Comment in: Chronic fatigue syndrome. [N J Med. 1992]

 

Source: Simpson LO. Chronic tiredness and idiopathic chronic fatigue–a connection? N J Med. 1992 Mar;89(3):211-6. http://www.ncbi.nlm.nih.gov/pubmed/1574202

 

Hypothesis: cytokines may be activated to cause depressive illness and chronic fatigue syndrome

Abstract:

Abnormalities in the regulation of the hypothalamo-pituitary-adrenal (HPA) axis are a well recognised feature of endogenous depression. The mechanism underlying this phenomenon remains obscure although there is strong evidence suggesting excessive CRH activity at the level of the hypothalamus.

We propose a novel hypothesis in which we suggest that the aetiological antecent to CRH hyperactivity is cytokine activation in the brain. It is now well established both that interleukins -1 and -6 are produced in a number of central loci and that cytokines are potent stimulators of the HPA axis.

Hence, we suggest that activation of IL-1 and IL-6 by specific mechanisms (such as neurotropic viral infection) in combination with the consequent CRH-41 stimulation, may (via their known biological effects) underly many of the features found in major depression and other related disorders, particularly where chronic fatigue is a prominent part of the symptom complex.

This theory has considerable heuristic value and suggests a number of experimental stratagems which may employed in order to confirm or reject it.

 

Source: Ur E, White PD, Grossman A. Hypothesis: cytokines may be activated to cause depressive illness and chronic fatigue syndrome. Eur Arch Psychiatry Clin Neurosci. 1992;241(5):317-22. http://www.ncbi.nlm.nih.gov/pubmed/1606197

 

The pathophysiology of chronic fatigue syndrome: confirmations, contradictions, and conjectures

Abstract:

OBJECTIVE: To examine published data regarding patient cohorts with the recently defined chronic fatigue syndrome.

METHOD: Review of thirty-two peer-assessed research publications that included full disclosure of the methodology employed; classification of the findings as confirmed, contradictory, or non-duplicated.

RESULTS: Research studies have confirmed that the majority of patients with the chronic fatigue syndrome: 1) are white middle-aged women, 2) have a high prevalence of current major depression and somatization disorder, 3) have abnormal personality traits, 4) believe that their fatigue has a physical cause, and 5) show mild abnormalities of humoral immunity. Contradictory data have been presented with regard to: 1) the time of onset of depressive disorders, 2) the etiologic role of herpetic and enteroviral infections, 3) the presence of abnormal cellular immunity, and 4) the clinical utility of immunoglobulin therapy. Non-duplicated research has indicated 1) hypothalamic-pituitary-adrenal axis dysfunction, 2) abnormalities on magnetic resonance images of the brain, 3) altered cytokine production, and 4) the possibility of retroviral infection.

CONCLUSIONS: As presently defined, the chronic fatigue syndrome has many of the clinical and biological features associated with depressive and somatoform disorders. A specific etiologic role for infections or immune dysfunction has not been confirmed.

 

Source: Manu P, Lane TJ, Matthews DA. The pathophysiology of chronic fatigue syndrome: confirmations, contradictions, and conjectures. Int J Psychiatry Med. 1992;22(4):397-408. http://www.ncbi.nlm.nih.gov/pubmed/1338059

 

Muscle biochemistry and pathophysiology in postviral fatigue syndrome

Abstract:

Patients with postviral fatigue syndrome (PVFS) usually complain of the skeletal muscle-related symptoms of fatigue and myalgia. It is not surprising therefore that the muscles have recently been the object of intensive studies which have used a variety of biochemical and physiological techniques. The aim of this chapter is to review these findings, and to discuss their significance or otherwise to the presenting symptoms and course of the condition.

 

Source: Edwards RH, Newham DJ, Peters TJ. Muscle biochemistry and pathophysiology in postviral fatigue syndrome. Br Med Bull. 1991 Oct;47(4):826-37. http://www.ncbi.nlm.nih.gov/pubmed/1794087