Category: Pathogenesis

Chronic fatigue syndrome

Abstract:

Chronic fatigue syndrome (CFS), which is characterized by devastating fatigue, mild fever, lymphadenopathy, headache, myalgia, insomnia and neuropsychiatric disorders, now has drawn much attentions from many physicians, researchers and even peoples in general society world wide. The pathogenesis of CFS is still remains to be clarified and clinico-pathological difference between CFS and mood disorder is controversial. In this paper, CFS would be reviewed in detail.

 

Source: Matsuda J. Chronic fatigue syndrome. Nihon Rinsho. 1992 Apr;50(4):887-91. [Article in Japanese] http://www.ncbi.nlm.nih.gov/pubmed/1619775

 

Psychiatric perspectives: an overview

Abstract:

This chapter reviews the evidence concerning the importance of psychological and social factors in the aetiology and pathogenesis of chronic fatigue syndrome. The diagnosis is often offered to doctors by patients; and we consider attribution, stigma, collusion between doctor and patient, and abnormal illness behaviour in this context. We then give a brief description of a model for common mental disorders, and show how chronic fatigue syndrome relates to this model. It emerges that there are special vulnerability factors in these patients’ personalities before the viral illness, but the disorder is seen as being released by the viral illness. By the time the disorder becomes established the original causal nexus is seen as no longer so important, and the disorder can be seen as a form of abnormal illness behaviour maintained by special factors. The implications for treatment are then considered.

 

Source: Woods TO, Goldberg DP. Psychiatric perspectives: an overview. r Med Bull. 1991 Oct;47(4):908-18. http://www.ncbi.nlm.nih.gov/pubmed/1794090

 

Myalgic encephalomyelitis

Comment on: Myalgic encephalomyelitis. [J R Soc Med. 1991]

 

The exchange of views between Drs Wessely and Wilson in the correspondence columns of the March issue of the Journal (March 1991 JRSM, p 182) highlights the divergence of opinion concerning the nature of myalgic encephalomyelitis (ME).

Recognition of ME as a significant health problem in New Zealand dates from an outbreak of ‘Tapanui ‘flu’ in a small country town in 1983. As it seemed possible that the wide range of symptoms could be indicative of impaired capillary blood flow, we studied the filtrability of blood samples from members of ME support groups. We found that subjects who were acutely unwell had prolonged blood filtration times which returned towards normal in the chronic state.

More recently it has been shown that ME symptoms are associated with increased percentages of nondiscocytic erythrocytes and the percentage of such cells showed an inverse correlation with wellbeing. The significance of altered red cell shape in the pathogenesis of ME has been discussed and it has been found that an injection of vitamin B12 improved wellbeing within 24 h. The loss of symptoms was associated with reduced percentages of nondiscocytes in about 50% of subjects. Those who failed to perceive a beneficial response from the B12 showed no change in red cell shape. Further studies at varying degrees of completion confirm and extend the published observations.

You can read the rest of this comment here: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1295578/pdf/jrsocmed00119-0075a.pdf

 

Source: Simpson LO. Myalgic encephalomyelitis. J R Soc Med. 1991 Oct;84(10):633. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1295578/

 

Amplification and identification of enteroviral sequences in the postviral fatigue syndrome

Abstract:

Evidence from several sources has long suggested that enteroviruses might play a role in the postviral fatigue syndrome (PVFS).

We used the most sensitive molecular virological method available at present, the polymerase chain reaction (PCR) amplification technique, to look for enteroviral copies in peripheral blood leucocytes and muscle from a well-defined group of patients. We demonstrated that our PCR method amplified a sequence common to a wide range of enteroviral serotypes. A highly significant number of the muscle biopsies (53%: P = less than 0.001) from the patients were positive for enteroviral sequences. With regard to the leucocyte samples, 16% in both patient and control were positive.

The PCR results on the peripheral blood leucocytes were in keeping with serological findings, in showing that the level of exposure to enteroviruses seemed to be the same in patients and controls: it was therefore of the greatest interest that patients were 6.7 times more likely to have enteroviral genome in their muscle.

We conclude that persistent enteroviral infection plays a role in the pathogenesis of PVFS, also providing preliminary evidence that severe mitochondrial injury is one of the mechanisms involved.

 

Source: Gow JW, Behan WM. Amplification and identification of enteroviral sequences in the postviral fatigue syndrome. Br Med Bull. 1991 Oct;47(4):872-85. http://www.ncbi.nlm.nih.gov/pubmed/1665380

 

Clinical and pathogenetic observations on children with chronic mononucleosis

Abstract:

Epstein-Barr virus is seldom the causative agent of a prolonged atypical illness, known as chronic mononucleosis syndrome, characterized by a persistent pattern of clinical manifestations and by a defective immune response to specific viral antigens. This paper refers about 6 children for whom clinical and serological findings suggest the chronic Epstein-Barr virus infection. The authors believe that this chronic state might be explained by the unusual antibody pattern to EBV virus, with the persistent presence of anti-EA and the absence of anti-EBNA titers, expression of a reduced EBV-specific cytotoxic T cell activity.

 

Source: Cataldo F, Ammatuna P, Bellia L, Sammartano F, Violante M, Albeggiani A. Clinical and pathogenetic observations on children with chronic mononucleosis. Pediatr Med Chir. 1991 Sep-Oct;13(5):489-94. [Article in Italian] http://www.ncbi.nlm.nih.gov/pubmed/1664943

 

Altered cytokine release in peripheral blood mononuclear cell cultures from patients with the chronic fatigue syndrome

Abstract:

Chronic fatigue syndrome (CFS) is an idiopathic illness associated with a variety of immunologic abnormalities. To investigate potential pathogenetic mechanisms, we evaluated serum levels and peripheral blood mononuclear cell (PBMC) production of selected cytokines and immunoglobulins.

Serum bioactive transforming growth factor beta (TGF-beta) levels were higher (P less than 0.01) in patients with CFS (290 +/- 46 pg/mL) than in control subjects (104 +/- 18 pg/mL), but levels of other cytokines tested were not different. Lipopolysaccharide-stimulated release of interleukin 1 beta (IL-1 beta), IL-6, and tumor necrosis factor-alpha was increased (P less than 0.05) in PBMC cultures from patients with CFS versus control subjects; enhanced (P less than 0.01) IL-6 release to phytohemagglutinin was also observed.

In contrast, TGF-beta release in response to lipopolysaccharide was depressed (P less than 0.01) in PBMC cultures derived from patients with CFS. No differences in IL-2 and IL-4 or immunoglobulin production were observed.

The enhanced release of inflammatory cytokines by stimulated PBMC from patients with CFS suggests that these cells are primed for an increased response to immune stimuli. These data also suggest an association between abnormal regulation of TGF-beta production in vivo and in vitro with the immunologic consequence of CFS.

 

Source: Chao CC1, Janoff EN, Hu SX, Thomas K, Gallagher M, Tsang M, Peterson PK. Altered cytokine release in peripheral blood mononuclear cell cultures from patients with the chronic fatigue syndrome. Cytokine. 1991 Jul;3(4):292-8. http://www.ncbi.nlm.nih.gov/pubmed/1873478

 

Muscle performance, voluntary activation, twitch properties and perceived effort in normal subjects and patients with the chronic fatigue syndrome

Abstract:

The decrease in maximal force-generating capacity, the degree of central activation of the muscle, and the subjective perception of effort were measured during prolonged submaximal isometric exercise in 12 male patients suffering from the ‘chronic fatigue syndrome’ and 13 naive, healthy male subjects.

Maximal voluntary isometric torque generated by the elbow flexors was measured before, and at 5 min intervals during an endurance sequence of 45 min of repetitive isometric contractions (6 s duration, 4 s rest interval) producing 30% of the initial maximal voluntary torque. Electrical stimuli were also delivered to the elbow flexors to measure the contractile force in the intervals between voluntary contractions. The degree of central motor activation during maximal voluntary contractions was assessed using a sensitive method of twitch interpolation.

In addition, the perceived effort required to achieve the target submaximal contractions was recorded using a standardized self-report scale. A high degree of central activation was achieved in maximal contractions during the endurance sequence both in the patients (mean of maximal force 93.6%; SD 7.8%), and in the control subjects (mean 90.9%; SD 9.5%).

The relative torque produced by either voluntary or electrically stimulated contractions was not significantly different between patients and control subjects throughout the test. There was no significant difference in the perceived exertion between the patients and control subjects.

These findings support the concept that neither poor motivation, nor muscle contractile failure is important in the pathogenesis of ‘fatigue’ in patients with the chronic fatigue syndrome.

 

Source: Lloyd AR, Gandevia SC, Hales JP. Muscle performance, voluntary activation, twitch properties and perceived effort in normal subjects and patients with the chronic fatigue syndrome. Brain. 1991 Feb;114 ( Pt 1A):85-98. http://www.ncbi.nlm.nih.gov/pubmed/1998892

 

Chronic fatigue syndrome: thoughts on pathogenesis

Abstract:

Studies have shown that a proportion of patients with severe chronic infection due to Epstein-Barr virus (EBV) lack antibody to a component of EBV nuclear antigen. However, it is not clear whether this circumstance is one of cause or effect in regard to the pathogenesis of chronic fatigue syndrome (CFS); it is clearly not pathognomonic since it also occurs in persons infected with the human immunodeficiency virus and–rarely–in those with other EBV-related conditions. Stress and depression may be other pathogenetic mechanisms that could reactivate EBV and lead to CFS; examples of this phenomenon are given. The syndrome might also follow certain other viral infections as part of a process that has been called postinfectious neurasthenia. Currently, the cause(s) and cure of CFS, a common and distressing syndrome, are enigmatic and require multidisciplinary study.

 

Source: Evans AS. Chronic fatigue syndrome: thoughts on pathogenesis. Rev Infect Dis. 1991 Jan-Feb;13 Suppl 1:S56-9. http://www.ncbi.nlm.nih.gov/pubmed/1850544

 

Detection of Epstein-Barr virus with molecular hybridization techniques

Abstract:

The cord-blood transformation assay remains the standard method for detecting Epstein-Barr virus (EBV) in secretions. However, newer methods are much faster and more sensitive, although most are still regarded as research procedures. The most useful of these are Southern blot hybridization, particularly the variation that employs terminal genomic probe analysis; in situ cytohybridization; and polymerase chain reaction analyses. Use of these methods alone or in combination should disclose the infected cell type, whether the infection is productive or latent, and the presence of multiple strains of EBV. Such information may help establish whether EBV is a causal agent in chronic fatigue syndrome.

 

Source: Pagano JS. Detection of Epstein-Barr virus with molecular hybridization techniques. Rev Infect Dis. 1991 Jan-Feb;13 Suppl 1:S123-8. http://www.ncbi.nlm.nih.gov/pubmed/1850538

 

A controlled trial of intravenous immunoglobulin G in chronic fatigue syndrome

Abstract:

PURPOSE: Currently, there is no established therapy for chronic fatigue syndrome (CFS), a recently defined illness that has been associated with a variety of immunologic abnormalities. Based on the hypothesis that a chronic viral infection or an immunoregulatory defect is involved in the pathogenesis of CFS, the therapeutic benefit of intravenous immunoglobulin G (IV IgG) was evaluated in a group of patients with CFS. Additionally, serum immunoglobulin concentrations and peripheral blood lymphocyte subset numbers were measured at the outset of the study, and the effect of IV IgG therapy on IgG subclass levels was determined.

PATIENTS AND METHODS: Thirty patients with CFS were enrolled in a double-blind, placebo-controlled trial of IV IgG. The treatment regimen consisted of IV IgG (1 g/kg) or intravenous placebo (1% albumin solution) administered every 30 days for 6 months. Participants completed a self-assessment form prior to each of the six treatments, which was used to measure severity of symptoms, functional status, and health perceptions. Patients were also asked to report adverse experiences defined as worsening of symptoms occurring within 48 hours of each treatment.

RESULTS: Twenty-eight patients completed the trial. At baseline, all 28 patients complained of moderate to severe fatigue, and measures of social functioning and health perceptions showed marked impairment. Low levels of IgG1 were found in 12 (42.9%), and 18 (64.3%) had low levels of IgG3. At the end of the study, no significant therapeutic benefit could be detected in terms of symptom amelioration or improvement in functional status, despite restoration of IgG1 levels to a normal range. Major adverse experiences were observed in 20% of both the IV IgG and placebo groups.

CONCLUSION: The results of this study indicate that IV IgG is unlikely to be of clinical benefit in CFS. In addition to the ongoing need for placebo-controlled trials of candidate therapies for CFS, an expanded research effort is needed to define the etiology and pathogenesis of this disorder.

Comment in:

Intravenous immunoglobulin treatment for the chronic fatigue syndrome. [Am J Med. 1990]

 

Source: Peterson PK, Shepard J, Macres M, Schenck C, Crosson J, Rechtman D, Lurie N. A controlled trial of intravenous immunoglobulin G in chronic fatigue syndrome. Am J Med. 1990 Nov;89(5):554-60. http://www.ncbi.nlm.nih.gov/pubmed/2239975